Is ABCA4 p.Ser765Asn (c.2294G>A) pathogenic?

ABCA4 p.Ser765Asn (c.2294G>A) is classified Pathogenic/Likely pathogenic in ABCA4 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-07-28). AlphaMissense: likely pathogenic (0.5845); Absent from gnomAD v4.1; Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Ser765Asn (c.2294G>A)?

ABCA4 p.Ser765Asn (c.2294G>A) is associated with ABCA4-related disorder, Stargardt disease (ClinVar).

How common is ABCA4 p.Ser765Asn (c.2294G>A) in the general population?

ABCA4 p.Ser765Asn (c.2294G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA4 p.Ser765Asn (c.2294G>A)?

AlphaMissense predicts likely pathogenic (score 0.5845) — an in-silico prediction, not a clinical call.

ABCA4 p.Ser765Asn

c.2294G>A · rs61749429 · VCV99125

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.5845 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ABCA4-related disorder

Computational evidence

Protein change
AlphaMissense	0.5845	likely pathogenic ✓ concordant with ClinVar
REVEL	0.63	indeterminate
SaProt	LLR -12.41	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	24.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCA4
Protein: p.Ser765Asn
Coding: c.2294G>A
MANE Select: NM_000350
dbSNP: rs61749429
Type: single nucleotide variant
Location: chr1:94056689 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 765: 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; likely pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and n-ret-pe-stimulated atpase activity below 50% of wild-type values; severely decreased n-all-trans-retinylidenephosphatidylethanolamine binding); a UniProt-annotated variant site (in stgd1; likely pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; severe decrease of basal and n-ret-pe-stimulated atpase activity; severely decreased n-all-trans-retinylidenephosphatidylethanolamine binding); an α-helix; a disulfide bond

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

Disease context

Also linked: Stargardt disease

Similar variants

ABCA4 p.Ser765Arg Pathogenic/Likely pathogenic ★★ same residue
ABCA4 p.Ser765Thr Pathogenic ★★ ⚠ same residue
ABCA4 c.4253+43G>A Pathogenic ★★★ same condition
ABCA4 c.4352+1G>A Pathogenic ★★★ same condition
ABCA4 c.5196+1137G>A Pathogenic ★★★ same condition
ABCA4 c.5460+1G>A Pathogenic ★★★ same condition
ABCA4 c.5461-10T>C Pathogenic ★★★ same condition
ABCA4 c.5714+5G>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-ser765asn (accessed [today's date]).

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