Is ABCA4 p.Pro1761Arg (c.5282C>G) pathogenic?

ABCA4 p.Pro1761Arg (c.5282C>G) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-08-16). AlphaMissense: likely benign (0.2535); Absent from gnomAD v4.1; Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Pro1761Arg (c.5282C>G)?

ABCA4 p.Pro1761Arg (c.5282C>G) is associated with ABCA4-related disorder (ClinVar).

How common is ABCA4 p.Pro1761Arg (c.5282C>G) in the general population?

ABCA4 p.Pro1761Arg (c.5282C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA4 p.Pro1761Arg (c.5282C>G)?

AlphaMissense predicts likely benign (score 0.2535) — an in-silico prediction, not a clinical call.

ABCA4 p.Pro1761Arg

c.5282C>G · rs1057520212 · VCV377405

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2535 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCA4-related disorder

Computational evidence

Protein change
AlphaMissense	0.2535	likely benign
REVEL	0.748	pathogenic-leaning
SaProt	LLR -11.57	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	26.5	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.Pro1761Arg
Coding: c.5282C>G
MANE Select: NM_000350
dbSNP: rs1057520212
Type: single nucleotide variant
Location: chr1:94015769 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1761: 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 and cord3; uncertain significance); a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (in stgd1 and ffm; uncertain significance); a UniProt-annotated variant site (in stgd1); an α-helix

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

Disease context

ABCA4-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA4 p.Pro1761Thr Uncertain significance ★ ⚠ same residue
ABCA4 p.Pro1761_Leu1763del Conflicting classifications of pathogenicity ★ same residue
ABCA4 c.1099+2T>G Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.160+5G>C Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.1937+1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.1938-619A>G Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.2160+1G>C Pathogenic ★★ same condition
ABCA4 c.2161-8G>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-pro1761arg (accessed [today's date]).

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