Is ABCA4 p.Pro927Ser (c.2779C>T) pathogenic?

ABCA4 p.Pro927Ser (c.2779C>T) is classified Uncertain significance in ABCA4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-31). AlphaMissense: likely benign (0.1966); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCA4 p.Pro927Ser (c.2779C>T)?

ABCA4 p.Pro927Ser (c.2779C>T) is associated with Inborn genetic diseases, Stargardt disease 3 (ClinVar).

How common is ABCA4 p.Pro927Ser (c.2779C>T) in the general population?

ABCA4 p.Pro927Ser (c.2779C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ABCA4 p.Pro927Ser (c.2779C>T)?

AlphaMissense predicts likely benign (score 0.1966) — an in-silico prediction, not a clinical call.

ABCA4 p.Pro927Ser

c.2779C>T · rs985690206 · VCV929304

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1966 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1966	likely benign
REVEL	0.49	indeterminate
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.97, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	22.2	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 0.00333% Admixed American · 2/60,024 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000205% 3/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,012
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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.Pro927Ser
Coding: c.2779C>T
MANE Select: NM_000350
dbSNP: rs985690206
Type: single nucleotide variant
Location: chr1:94047058 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 927: 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 β-strand; a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Stargardt disease 3

Similar variants

ABCA4 p.Pro927= Likely benign ★ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
ABCA4 p.Arg212Cys Pathogenic ★★★ ⚠ same condition
ABCA4 p.Arg408Ter Pathogenic ★★★ same condition
ABCA4 p.Arg602Trp Pathogenic ★★★ same condition
ABCA4 p.Arg681Ter Pathogenic ★★★ same condition
ABCA4 p.Asn965Ser Pathogenic ★★★ same condition
ABCA4 p.Gly863Ala Uncertain significance ★★★ ⚠ 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-pro927ser (accessed [today's date]).

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