Is ABCB11 p.Arg313Cys (c.937C>T) pathogenic?

ABCB11 p.Arg313Cys (c.937C>T) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-27). AlphaMissense: likely benign (0.1109); Very rare (popmax 0.00267%, afr).

How common is ABCB11 p.Arg313Cys (c.937C>T) in the general population?

ABCB11 p.Arg313Cys (c.937C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ABCB11 p.Arg313Cys (c.937C>T)?

AlphaMissense predicts likely benign (score 0.1109) — an in-silico prediction, not a clinical call.

ABCB11 p.Arg313Cys

c.937C>T · rs375087680 · VCV595167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1109	likely benign
REVEL	0.665	pathogenic-leaning
SaProt	LLR -10.51	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.8	GERP 1.2, phastCons 1
Overall
CADD	25.8	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 0.00267% African / African-American · 2/74,836 alleles

Filtering AF 0.000764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.0013% 21/1,612,744 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,418
South Asian	0.0022%	45,518
Admixed American	0.00167%	59,902
Remaining individualsnot grpmax-eligible	0.0016%	62,396
European (non-Finnish)	0.00127%	78,633

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.Arg313Cys
Coding: c.937C>T
MANE Select: NM_003742
dbSNP: rs375087680
Type: single nucleotide variant
Location: chr2:168986256 (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

Similar variants

ABCB11 p.Arg313Ser Uncertain significance ★★ ⚠ same residue
ABCB11 p.Arg313His Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCB11 p.Arg313Leu Uncertain significance ★ ⚠ same residue
ABCB11 p.Arg313= Likely benign ★ same residue
ABCB11 c.1084-2A>G Pathogenic ★★ same type
ABCB11 c.1197+1G>T Pathogenic/Likely pathogenic ★★ same type
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same type
ABCB11 c.1198-2A>C 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/abcb11-p-arg313cys (accessed [today's date]).

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