Is ABCA13 p.Ser2256Pro (c.6766T>C) pathogenic?

ABCA13 p.Ser2256Pro (c.6766T>C) is classified Likely benign in ABCA13 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: likely benign (0.0472); Ultra-rare (popmax 0.0129%, amr).

How common is ABCA13 p.Ser2256Pro (c.6766T>C) in the general population?

ABCA13 p.Ser2256Pro (c.6766T>C) is ultra-rare (popmax 0.0129%, amr) (gnomAD).

What do computational predictors say about ABCA13 p.Ser2256Pro (c.6766T>C)?

AlphaMissense predicts likely benign (score 0.0472) — an in-silico prediction, not a clinical call.

ABCA13 p.Ser2256Pro

c.6766T>C · rs956783034 · VCV2302279

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0472 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0129%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0472	likely benign
REVEL	0.112	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.39	GERP -1.7
Regional constraint	o/e 1.03	unconstrained · MANE · 205 kb · p 0.083 · regional, not allelic
Overall
CADD	0.255	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 0.0129% Admixed American · 7/54,304 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00423%

Overall 0.000635% 10/1,574,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0129%	7,758
Remaining individualsnot grpmax-eligible	0.00165%	60,652
South Asian	0.0012%	83,562
European (non-Finnish)	8.6e-05%	1,162,179

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: ABCA13
Protein: p.Ser2256Pro
Coding: c.6766T>C
MANE Select: NM_152701
dbSNP: rs956783034
Type: single nucleotide variant
Location: chr7:48276432 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI <0.01 (gnomAD)

Full ABCA13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA13 p.Ala1627Val Uncertain significance ★★ ⚠ same type
ABCA13 p.Ala4240Thr Uncertain significance ★★ ⚠ same type
ABCA13 c.1263-5C>G Benign/Likely benign ★★ same type
ABCA13 p.Ala2178Glu Benign ★★ same type
ABCA13 p.Ala922Thr Benign ★★ same type
ABCA13 p.Arg4043Cys Benign ★★ same type
ABCA13 p.Arg4070Cys Benign ★★ same type
ABCA13 p.Arg4681Gln Likely benign ★★ 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/abca13-p-ser2256pro (accessed [today's date]).

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