Is ABCA4 p.Ala1038Val (c.3113C>T) pathogenic?

ABCA4 p.Ala1038Val (c.3113C>T) is classified Pathogenic/Likely pathogenic in ABCA4 (ClinVar, Multiple submitters, 39 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1637); Rare (popmax 0.205%, nfe); Associated with retinitis pigmentosa 19.

What condition is associated with ABCA4 p.Ala1038Val (c.3113C>T)?

ABCA4 p.Ala1038Val (c.3113C>T) is associated with retinitis pigmentosa 19, optic atrophy, retinal disorder (ClinVar).

How common is ABCA4 p.Ala1038Val (c.3113C>T) in the general population?

ABCA4 p.Ala1038Val (c.3113C>T) is rare (popmax 0.205%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCA4 p.Ala1038Val (c.3113C>T)?

AlphaMissense predicts likely benign (score 0.1637) — an in-silico prediction, not a clinical call.

ABCA4 p.Ala1038Val

c.3113C>T · rs61751374 · VCV7894

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 39 submitters

AlphaMissense

likely benign

0.1637 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.205%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

retinitis pigmentosa 19

Computational evidence

Protein change
AlphaMissense	0.1637	likely benign ⚠ discordant with ClinVar
REVEL	0.533	indeterminate
SaProt	LLR -13.84	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 0.77, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.205% European (non-Finnish) · 2,423/1,180,038 alleles

Filtering AF 0.198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.196%

Overall 0.185% 2,983/1,614,144 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.551%	181
European (non-Finnish)grpmax	0.205%	487
Remaining individualsnot grpmax-eligible	0.168%	595
Admixed American	0.11%	909
African / African-American	0.0333%	3,001
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,402
South Asian	0.00769%	13,011

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCA4
Protein: p.Ala1038Val
Coding: c.3113C>T
MANE Select: NM_000350
dbSNP: rs61751374
Type: single nucleotide variant
Location: chr1:94043413 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1038: a UniProt-annotated variant site (in cord3; uncertain significance); a UniProt-annotated variant site (in stgd1; uncertain significance); a UniProt-annotated variant site (found in a patient with chorioretinal atrophy; uncertain significance); a UniProt-annotated variant site (found in a patient with macular dystrophy; uncertain significance); a UniProt-annotated variant site (in stgd1, ffm and cord3; pathogenic; common variant; decreased solubility; does not affect intracellular vesicle localization; significantly reduces n-all-trans-retinylidenephosphatidylethanolamine binding; severely reduces basal and n-ret-pe-stimulated atpase activity); the abc transporter 1 domain; an α-helix; a disulfide bond

Full ABCA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 19 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: optic atrophy retinal disorder age related macular degeneration 2 severe early-childhood-onset retinal dystrophy cone-rod dystrophy 3 inherited retinal dystrophy retinitis pigmentosa Stargardt disease

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ABCA4 p.Ala1038= Likely benign ★ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
ABCA4 c.3523-1G>A Pathogenic ★★★ same condition
ABCA4 c.4253+43G>A Pathogenic ★★★ same condition
ABCA4 c.4254-1G>C Pathogenic ★★★ same condition
ABCA4 c.4352+1G>A Pathogenic ★★★ same condition
ABCA4 c.4773+3A>G Pathogenic ★★★ same condition
ABCA4 c.5018+2T>A Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abca4-p-ala1038val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown