Is ABCC10 p.Val635Phe (c.1903G>T) pathogenic?

ABCC10 p.Val635Phe (c.1903G>T) is classified Uncertain significance in ABCC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely pathogenic (0.838); Very rare (popmax 0.00334%, amr).

How common is ABCC10 p.Val635Phe (c.1903G>T) in the general population?

ABCC10 p.Val635Phe (c.1903G>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about ABCC10 p.Val635Phe (c.1903G>T)?

AlphaMissense predicts likely pathogenic (score 0.838) — an in-silico prediction, not a clinical call.

ABCC10 p.Val635Phe

c.1903G>T · VCV4114064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.838	likely pathogenic · top 9% in ABCC10
REVEL	0.882	moderately pathogenic-leaning
SaProt	LLR -11.90	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 22 kb · p 4.2e-06 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00334% Admixed American · 2/59,906 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000744% 12/1,613,222 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,953
Remaining individualsnot grpmax-eligible	0.0016%	62,438
Finnishnot grpmax-eligible	0.00156%	63,980
European (non-Finnish)	0.000678%	147,471

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.Val635Phe
Coding: c.1903G>T
MANE Select: NM_001198934
Type: single nucleotide variant
Location: chr6:43437961 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32
Residue 635: the abc transporter 1 domain; a binding site

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-val635phe (accessed [today's date]).

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