Is ABCA4 p.Cys230Phe (c.689G>T) pathogenic?

ABCA4 p.Cys230Phe (c.689G>T) is classified Likely pathogenic in ABCA4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely pathogenic (0.7434); Absent from gnomAD v4.1; Associated with Stargardt disease.

What condition is associated with ABCA4 p.Cys230Phe (c.689G>T)?

ABCA4 p.Cys230Phe (c.689G>T) is associated with Stargardt disease (ClinVar).

How common is ABCA4 p.Cys230Phe (c.689G>T) in the general population?

ABCA4 p.Cys230Phe (c.689G>T) is absent from gnomAD v4.1 (gnomAD).

How is Stargardt disease inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCA4 p.Cys230Phe (c.689G>T)?

AlphaMissense predicts likely pathogenic (score 0.7434) — an in-silico prediction, not a clinical call.

ABCA4 p.Cys230Phe

c.689G>T · rs2523965931 · VCV1804176

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7434 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Stargardt disease

Computational evidence

Protein change
AlphaMissense	0.7434	likely pathogenic ✓ concordant with ClinVar
REVEL	0.945	strongly pathogenic-leaning
SaProt	LLR -12.49	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 4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	24.9	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.Cys230Phe
Coding: c.689G>T
MANE Select: NM_000350
dbSNP: rs2523965931
Type: single nucleotide variant
Location: chr1:94098873 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 230: 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 (in stgd1); a disulfide bond

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

Disease context

Stargardt disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Stargardt disease (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ABCA4 p.Cys230Ser Pathogenic ★★ ⚠ same residue
ABCA4 p.Cys230Tyr Likely 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-cys230phe (accessed [today's date]).

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