Is ABCB4 p.Ala791Ser (c.2371G>T) pathogenic?

ABCB4 p.Ala791Ser (c.2371G>T) is classified Uncertain significance in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-10). AlphaMissense: likely benign (0.1399); Rare (popmax 0.172%, eas); Associated with ABCB4-related disorder.

What condition is associated with ABCB4 p.Ala791Ser (c.2371G>T)?

ABCB4 p.Ala791Ser (c.2371G>T) is associated with ABCB4-related disorder (ClinVar).

How common is ABCB4 p.Ala791Ser (c.2371G>T) in the general population?

ABCB4 p.Ala791Ser (c.2371G>T) is rare (popmax 0.172%, eas) (gnomAD).

What do computational predictors say about ABCB4 p.Ala791Ser (c.2371G>T)?

AlphaMissense predicts likely benign (score 0.1399) — an in-silico prediction, not a clinical call.

ABCB4 p.Ala791Ser

c.2371G>T · rs753155827 · VCV2628516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1399 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.172%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ABCB4-related disorder

Computational evidence

Protein change
AlphaMissense	0.1399	likely benign
REVEL	0.41	indeterminate
SaProt	LLR -8.53	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 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.53 · regional, not allelic
Overall
CADD	22.2	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 0.172% East Asian · 77/44,874 alleles

Filtering AF 0.141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.00502% 81/1,614,104 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.172%	583
Remaining individualsnot grpmax-eligible	0.0016%	62,510
South Asian	0.0011%	91,082
European (non-Finnish)	0.000169%	589,984

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.Ala791Ser
Coding: c.2371G>T
MANE Select: NM_000443
dbSNP: rs753155827
Type: single nucleotide variant
Location: chr7:87420021 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 791: an α-helix; the abc transmembrane type-1 2 domain

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

Disease context

ABCB4-related disorder

Similar variants

ABCB4 p.Ala791Asp Uncertain significance ★ ⚠ same residue
ABCB4 c.2211+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.286+1G>A Pathogenic ★★ same condition
ABCB4 c.3486+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Arg1046Ter Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Arg176Trp Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Arg406Ter Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Arg47Ter Pathogenic ★★ same condition

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-ala791ser (accessed [today's date]).

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