Is ABCB10 p.Pro312Ser (c.934C>T) pathogenic?

ABCB10 p.Pro312Ser (c.934C>T) is classified Uncertain significance in ABCB10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: ambiguous (0.3762); Ultra-rare (popmax 0.0174%, afr).

How common is ABCB10 p.Pro312Ser (c.934C>T) in the general population?

ABCB10 p.Pro312Ser (c.934C>T) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about ABCB10 p.Pro312Ser (c.934C>T)?

AlphaMissense predicts ambiguous (score 0.3762) — an in-silico prediction, not a clinical call.

ABCB10 p.Pro312Ser

c.934C>T · VCV3971411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3762 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3762	ambiguous
REVEL	0.76	pathogenic-leaning
SaProt	LLR -8.61	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 40 kb · p 1.5e-09 · regional, not allelic
Overall
CADD	25.0	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 0.0174% African / African-American · 13/74,678 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00815%

Overall 0.00161% 26/1,611,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,744
Admixed American	0.00169%	59,196
Remaining individualsnot grpmax-eligible	0.0016%	62,358
European (non-Finnish)	0.000933%	107,211

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.Pro312Ser
Coding: c.934C>T
MANE Select: NM_012089
Type: single nucleotide variant
Location: chr1:229542359 (GRCh38)
Gene constraint: LOEUF 1.142 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.37 · 6 PDB
Residue 312: 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.Ala300Pro 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

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-pro312ser (accessed [today's date]).

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