Is ABCB10 p.Ala300Pro (c.898G>C) pathogenic?

ABCB10 p.Ala300Pro (c.898G>C) is classified Uncertain significance in ABCB10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely pathogenic (0.9927); Ultra-rare (popmax 0.0413%, afr).

How common is ABCB10 p.Ala300Pro (c.898G>C) in the general population?

ABCB10 p.Ala300Pro (c.898G>C) is ultra-rare (popmax 0.0413%, afr) (gnomAD).

What do computational predictors say about ABCB10 p.Ala300Pro (c.898G>C)?

AlphaMissense predicts likely pathogenic (score 0.9927) — an in-silico prediction, not a clinical call.

ABCB10 p.Ala300Pro

c.898G>C · VCV3971237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9927 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0413%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9927	likely pathogenic · top 1% in ABCB10
REVEL	0.671	pathogenic-leaning
SaProt	LLR -16.04	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 40 kb · p 1.5e-09 · regional, not allelic
Overall
CADD	25.9	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 0.0413% African / African-American · 31/75,010 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00242% 39/1,613,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0413%	2,420
Admixed American	0.00833%	12,005
Remaining individualsnot grpmax-eligible	0.00481%	20,808

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.Ala300Pro
Coding: c.898G>C
MANE Select: NM_012089
Type: single nucleotide variant
Location: chr1:229547522 (GRCh38)
Gene constraint: LOEUF 1.142 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.37 · 6 PDB
Residue 300: 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.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.Ala388Gly Uncertain significance ★ ⚠ same type
ABCB10 p.Ala394Thr Uncertain significance ★ ⚠ same type
ABCB10 p.Ala461Val Uncertain significance ★ ⚠ same type
ABCB10 p.Ala503Asp 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-ala300pro (accessed [today's date]).

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