Is ABCA10 p.Ala749Val (c.2246C>T) pathogenic?

ABCA10 p.Ala749Val (c.2246C>T) is classified Uncertain significance in ABCA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely benign (0.0887); Very rare (popmax 0.00668%, afr).

How common is ABCA10 p.Ala749Val (c.2246C>T) in the general population?

ABCA10 p.Ala749Val (c.2246C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about ABCA10 p.Ala749Val (c.2246C>T)?

AlphaMissense predicts likely benign (score 0.0887) — an in-silico prediction, not a clinical call.

ABCA10 p.Ala749Val

c.2246C>T · rs753872789 · VCV2473091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0887 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0887	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.5
Regional constraint	o/e 0.95	unconstrained · MANE · 77 kb · p 0.045 · regional, not allelic
Overall
CADD	0.054	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,904 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000744% 12/1,613,772 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,981
Admixed American	0.00333%	29,996
European (non-Finnish)	0.000424%	235,965

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: ABCA10
Protein: p.Ala749Val
Coding: c.2246C>T
MANE Select: NM_001377321
dbSNP: rs753872789
Type: single nucleotide variant
Location: chr17:69187765 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.70

Full ABCA10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA10 p.Ala1181Val Uncertain significance ★ ⚠ same type
ABCA10 p.Ala1187Val Uncertain significance ★ ⚠ same type
ABCA10 p.Ala1307Val Uncertain significance ★ ⚠ same type
ABCA10 p.Ala1335Pro Uncertain significance ★ ⚠ same type
ABCA10 p.Ala1461Thr Uncertain significance ★ ⚠ same type
ABCA10 p.Ala244Ser Uncertain significance ★ ⚠ same type
ABCA10 p.Ala424Val Uncertain significance ★ ⚠ same type
ABCA10 p.Ala760Thr Uncertain significance ★ ⚠ 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/abca10-p-ala749val (accessed [today's date]).

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