Is ABCA4 p.Arg290Pro (c.869G>C) pathogenic?

ABCA4 p.Arg290Pro (c.869G>C) is classified Likely pathogenic in ABCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-06). AlphaMissense: ambiguous (0.4323); Absent from gnomAD v4.1; Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Arg290Pro (c.869G>C)?

ABCA4 p.Arg290Pro (c.869G>C) is associated with ABCA4-related disorder (ClinVar).

How common is ABCA4 p.Arg290Pro (c.869G>C) in the general population?

ABCA4 p.Arg290Pro (c.869G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA4 p.Arg290Pro (c.869G>C)?

AlphaMissense predicts ambiguous (score 0.4323) — an in-silico prediction, not a clinical call.

ABCA4 p.Arg290Pro

c.869G>C · VCV4900771

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4323 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ABCA4-related disorder

Computational evidence

Protein change
AlphaMissense	0.4323	ambiguous
REVEL	0.581	indeterminate
SaProt	LLR -12.92	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	11.51	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.Arg290Pro
Coding: c.869G>C
MANE Select: NM_000350
Type: single nucleotide variant
Location: chr1:94080708 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 290: 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 disulfide bond

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.Arg290= Conflicting classifications of pathogenicity ★ same residue
ABCA4 p.Arg290Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA4 p.Arg290Trp 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

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-arg290pro (accessed [today's date]).

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