Is ABCA4 p.Ser795Arg (c.2385C>G) pathogenic?

ABCA4 p.Ser795Arg (c.2385C>G) is classified Likely pathogenic in ABCA4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-14). AlphaMissense: likely pathogenic (0.9827); Very rare (popmax 8.47e-05%, nfe); Associated with Generalized choriocapillaris dystrophy.

What condition is associated with ABCA4 p.Ser795Arg (c.2385C>G)?

ABCA4 p.Ser795Arg (c.2385C>G) is associated with Generalized choriocapillaris dystrophy (ClinVar).

How common is ABCA4 p.Ser795Arg (c.2385C>G) in the general population?

ABCA4 p.Ser795Arg (c.2385C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ABCA4 p.Ser795Arg (c.2385C>G)?

AlphaMissense predicts likely pathogenic (score 0.9827) — an in-silico prediction, not a clinical call.

ABCA4 p.Ser795Arg

c.2385C>G · rs1660946056 · VCV973687

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Generalized choriocapillaris dystrophy

Computational evidence

Protein change
AlphaMissense	0.9827	likely pathogenic ✓ concordant with ClinVar · top 2% in ABCA4
REVEL	0.715	pathogenic-leaning
SaProt	LLR -16.22	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 1.3	GERP 0.15, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	20.8	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 8.47e-05% European (non-Finnish) · 1/1,180,006 alleles

Overall 6.2e-05% 1/1,614,006 alleles · very rare exomes 1/1,461,730 · genomes 0/152,276 · joint denominator

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.Ser795Arg
Coding: c.2385C>G
MANE Select: NM_000350
dbSNP: rs1660946056
Type: single nucleotide variant
Location: chr1:94055313 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 795: 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)

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

Disease context

Generalized choriocapillaris dystrophy

Similar variants

ABCA4 p.Ser795Asn Pathogenic/Likely pathogenic ★★ same residue
ABCA4 p.Arg2030Ter Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Ser795fs Pathogenic ★★ same residue
ABCA4 p.Leu421= Conflicting classifications of pathogenicity ★ same condition
ABCA4 p.Met1777Val Conflicting classifications of pathogenicity ★ ⚠ same condition
ABCA4 p.Glu898fs Pathogenic ★★ same condition
ABCA4 p.Asn14fs Pathogenic ★ same condition
ABCA4 c.1937+1G>A Pathogenic ★★★ same type

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-ser795arg (accessed [today's date]).

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