Is ABCC10 p.Val294Met (c.880G>A) pathogenic?

ABCC10 p.Val294Met (c.880G>A) is classified Uncertain significance in ABCC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.0939); Ultra-rare (popmax 0.056%, sas).

How common is ABCC10 p.Val294Met (c.880G>A) in the general population?

ABCC10 p.Val294Met (c.880G>A) is ultra-rare (popmax 0.056%, sas) (gnomAD).

What do computational predictors say about ABCC10 p.Val294Met (c.880G>A)?

AlphaMissense predicts likely benign (score 0.0939) — an in-silico prediction, not a clinical call.

ABCC10 p.Val294Met

c.880G>A · rs202203665 · VCV3127478

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0939 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0939	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.82, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 22 kb · p 4.2e-06 · regional, not allelic
Overall
CADD	21.7	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 0.056% South Asian · 51/91,094 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.0149% 240/1,614,090 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.056%	1,786
Middle Eastern	0.0493%	2,028
Remaining individualsnot grpmax-eligible	0.0176%	5,681
European (non-Finnish)	0.0146%	6,861
Admixed American	0.00333%	30,003
African / African-American	0.00133%	74,930

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: ABCC10
Protein: p.Val294Met
Coding: c.880G>A
MANE Select: NM_001198934
dbSNP: rs202203665
Type: single nucleotide variant
Location: chr6:43432860 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32
Residue 294: the abc transmembrane type-1 1 domain

Full ABCC10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC10 p.Met895Thr Uncertain significance ★★ ⚠ same type
ABCC10 p.Ala1050Ser Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1119Thr Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1165Thr Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1179Thr Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1324Pro Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1324Ser Uncertain significance ★ ⚠ same type
ABCC10 p.Ala144Gly 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/abcc10-p-val294met (accessed [today's date]).

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