Is ABCB10 p.Val428Met (c.1282G>A) pathogenic?

ABCB10 p.Val428Met (c.1282G>A) is classified Uncertain significance in ABCB10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: ambiguous (0.3999); Very rare (popmax 0.00988%, sas).

How common is ABCB10 p.Val428Met (c.1282G>A) in the general population?

ABCB10 p.Val428Met (c.1282G>A) is very rare (popmax 0.00988%, sas) (gnomAD).

What do computational predictors say about ABCB10 p.Val428Met (c.1282G>A)?

AlphaMissense predicts ambiguous (score 0.3999) — an in-silico prediction, not a clinical call.

ABCB10 p.Val428Met

c.1282G>A · rs771905549 · VCV3119056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Computational evidence

Protein change
AlphaMissense	0.3999	ambiguous
REVEL	0.638	indeterminate
SaProt	LLR -11.12	damaging
Splicing
SpliceAI	Δ0.61	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 3.9	GERP 0.46, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 40 kb · p 1.5e-09 · regional, not allelic
Overall
CADD	26.2	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 0.00988% South Asian · 9/91,074 alleles

Filtering AF 0.00697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00694% 112/1,613,920 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,119
European (non-Finnish)	0.00831%	12,040
Admixed American	0.00333%	29,999
Remaining individualsnot grpmax-eligible	0.0032%	31,234
East Asian	0.00223%	44,900

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: ABCB10
Protein: p.Val428Met
Coding: c.1282G>A
MANE Select: NM_012089
dbSNP: rs771905549
Type: single nucleotide variant
Location: chr1:229539513 (GRCh38)
Gene constraint: LOEUF 1.142 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.37 · 6 PDB
Residue 428: the abc transmembrane type-1 domain; an α-helix

Full ABCB10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB10 p.Val428Gly Uncertain significance ★ ⚠ same residue
ABCB10 p.Asn478Lys Benign ★★ same type
ABCB10 p.Thr179= Benign ★★ same type
ABCB10 p.Ala110Pro Uncertain significance ★ ⚠ same type
ABCB10 p.Ala280Val Uncertain significance ★ ⚠ same type
ABCB10 p.Ala300Pro Uncertain significance ★ ⚠ same type
ABCB10 p.Ala388Gly Uncertain significance ★ ⚠ same type
ABCB10 p.Ala394Thr 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/abcb10-p-val428met (accessed [today's date]).

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