Is ABCB4 p.Ala310Thr (c.928G>A) pathogenic?

ABCB4 p.Ala310Thr (c.928G>A) is classified Uncertain significance in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-03). AlphaMissense: likely benign (0.1379); Ultra-rare (popmax 0.0483%, sas).

How common is ABCB4 p.Ala310Thr (c.928G>A) in the general population?

ABCB4 p.Ala310Thr (c.928G>A) is ultra-rare (popmax 0.0483%, sas) (gnomAD).

What do computational predictors say about ABCB4 p.Ala310Thr (c.928G>A)?

AlphaMissense predicts likely benign (score 0.1379) — an in-silico prediction, not a clinical call.

ABCB4 p.Ala310Thr

c.928G>A · rs747932250 · VCV501865

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1379 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1379	likely benign
REVEL	0.555	indeterminate
SaProt	LLR -7.36	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 2.7	GERP 1, phastCons 0.99
Regional constraint	o/e 0.74	unconstrained · MANE · 31 kb · p 4.4e-11 · regional, not allelic
Overall
CADD	23.0	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 0.0483% South Asian · 44/91,070 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00285% 46/1,613,558 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0483%	2,070
African / African-American	0.00267%	37,443

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: ABCB4
Protein: p.Ala310Thr
Coding: c.928G>A
MANE Select: NM_000443
dbSNP: rs747932250
Type: single nucleotide variant
Location: chr7:87447111 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 310: an α-helix; the abc transmembrane type-1 1 domain

Full ABCB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB4 p.Ala310= Likely benign ★ same residue
ABCB4 c.1006-2A>C Pathogenic ★★ same type
ABCB4 c.1356+2T>C Pathogenic/Likely pathogenic ★★ same type
ABCB4 c.1560+1G>A Likely pathogenic ★★ same type
ABCB4 c.2064+3A>T Likely pathogenic ★★ same type
ABCB4 c.2211+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCB4 c.2682+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCB4 c.2783+1G>T Pathogenic/Likely pathogenic ★★ 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/abcb4-p-ala310thr (accessed [today's date]).

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