Is ABCA4 p.Asp1102Val (c.3305A>T) pathogenic?

ABCA4 p.Asp1102Val (c.3305A>T) is classified Pathogenic in ABCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-10). AlphaMissense: likely pathogenic (0.8437); Very rare (popmax 0.000678%, nfe).

How common is ABCA4 p.Asp1102Val (c.3305A>T) in the general population?

ABCA4 p.Asp1102Val (c.3305A>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about ABCA4 p.Asp1102Val (c.3305A>T)?

AlphaMissense predicts likely pathogenic (score 0.8437) — an in-silico prediction, not a clinical call.

ABCA4 p.Asp1102Val

c.3305A>T · rs143689372 · VCV938220

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8437 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8437	likely pathogenic ✓ concordant with ClinVar
REVEL	0.956	strongly pathogenic-leaning
SaProt	LLR -12.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	27.2	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 0.000678% European (non-Finnish) · 8/1,180,038 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,614,056 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)grpmax	0.000678%	147,505

Remaining individuals 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.Asp1102Val
Coding: c.3305A>T
MANE Select: NM_000350
dbSNP: rs143689372
Type: single nucleotide variant
Location: chr1:94042784 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1102: 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); the abc transporter 1 domain; a UniProt-annotated variant site (in); an α-helix; a disulfide bond

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

Similar variants

ABCA4 p.Asp1102Tyr Pathogenic/Likely pathogenic ★★ same residue
ABCA4 p.Asp1102Ala Uncertain significance ★ ⚠ same residue
ABCA4 p.Asp1102Asn Conflicting classifications of pathogenicity ★ same residue
ABCA4 p.Asp1102Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same type
ABCA4 c.3328+2T>A Pathogenic ★★★ same type
ABCA4 c.3523-1G>A Pathogenic ★★★ same type
ABCA4 c.4253+43G>A Pathogenic ★★★ same type

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-asp1102val (accessed [today's date]).

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