Is ABCA4 p.Ala64Val (c.191C>T) pathogenic?

ABCA4 p.Ala64Val (c.191C>T) is classified Likely pathogenic in ABCA4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-29). AlphaMissense: likely benign (0.2055); Very rare (popmax 0.000847%, nfe); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Ala64Val (c.191C>T)?

ABCA4 p.Ala64Val (c.191C>T) is associated with ABCA4-related disorder, Stargardt disease (ClinVar).

How common is ABCA4 p.Ala64Val (c.191C>T) in the general population?

ABCA4 p.Ala64Val (c.191C>T) is very rare (popmax 0.000847%, nfe) (gnomAD).

What do computational predictors say about ABCA4 p.Ala64Val (c.191C>T)?

AlphaMissense predicts likely benign (score 0.2055) — an in-silico prediction, not a clinical call.

ABCA4 p.Ala64Val

c.191C>T · rs1388219872 · VCV2733951

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCA4-related disorder

Computational evidence

Protein change
AlphaMissense	0.2055	likely benign ⚠ discordant with ClinVar
REVEL	0.884	moderately pathogenic-leaning
SaProt	LLR -7.17	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	28.2	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 0.000847% European (non-Finnish) · 10/1,180,036 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.00062% 10/1,614,114 alleles · very rare

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.Ala64Val
Coding: c.191C>T
MANE Select: NM_000350
dbSNP: rs1388219872
Type: single nucleotide variant
Location: chr1:94111549 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 64: an α-helix; a disulfide bond; a UniProt-annotated variant site (in stgd1; uncertain significance); a UniProt-annotated variant site (in cord3; uncertain significance)

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

Disease context

Also linked: Stargardt disease

Similar variants

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ABCA4 c.5714+5G>A Pathogenic ★★★ same condition
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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-ala64val (accessed [today's date]).

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