Is ABCB11 p.Arg313His (c.938G>A) pathogenic?

ABCB11 p.Arg313His (c.938G>A) is classified Conflicting classifications of pathogenicity in ABCB11 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-03). AlphaMissense: likely benign (0.0708); Very rare (popmax 0.00373%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCB11 p.Arg313His (c.938G>A)?

ABCB11 p.Arg313His (c.938G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB11 p.Arg313His (c.938G>A) in the general population?

ABCB11 p.Arg313His (c.938G>A) is very rare (popmax 0.00373%, nfe) (gnomAD).

What do computational predictors say about ABCB11 p.Arg313His (c.938G>A)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

ABCB11 p.Arg313His

c.938G>A · rs372175341 · VCV2169786

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -7.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.052	GERP -1.4, phastCons 0.025
Overall
CADD	17.75	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 0.00373% European (non-Finnish) · 44/1,179,526 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00298% 48/1,612,850 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00373%	26,807
East Asian	0.00223%	44,850
Admixed American	0.00167%	59,906
African / African-American	0.00134%	74,860
South Asian	0.0011%	91,042

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: ABCB11
Protein: p.Arg313His
Coding: c.938G>A
MANE Select: NM_003742
dbSNP: rs372175341
Type: single nucleotide variant
Location: chr2:168986255 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.23 · 9 PDB
Residue 313: an α-helix; the abc transmembrane type-1 1 domain

Full ABCB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCB11 p.Arg313Ser Uncertain significance ★★ ⚠ same residue
ABCB11 p.Arg313Cys Uncertain significance ★ ⚠ same residue
ABCB11 p.Arg313Leu Uncertain significance ★ ⚠ same residue
ABCB11 p.Arg313= Likely benign ★ same residue
ABCB11 p.Ala1283Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Ala693Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Asp1236Tyr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Cys1117Tyr Uncertain significance ★★ ⚠ 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/abcb11-p-arg313his (accessed [today's date]).

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