Is ABCB11 p.Arg313Ser (c.937C>A) pathogenic?

ABCB11 p.Arg313Ser (c.937C>A) is classified Uncertain significance in ABCB11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-14). AlphaMissense: likely benign (0.1911); Very rare (popmax 0.00153%, nfe); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Arg313Ser (c.937C>A)?

ABCB11 p.Arg313Ser (c.937C>A) is associated with familial intrahepatic cholestasis, progressive familial intrahepatic cholestasis type 2 (ClinVar).

How common is ABCB11 p.Arg313Ser (c.937C>A) in the general population?

ABCB11 p.Arg313Ser (c.937C>A) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about ABCB11 p.Arg313Ser (c.937C>A)?

AlphaMissense predicts likely benign (score 0.1911) — an in-silico prediction, not a clinical call.

ABCB11 p.Arg313Ser

c.937C>A · VCV3776873

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1911 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
AlphaMissense	0.1911	likely benign
REVEL	0.389	indeterminate
SaProt	LLR -6.81	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
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	21.6	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 0.00153% European (non-Finnish) · 18/1,179,498 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,612,744 alleles · very rare exomes 15/1,460,714 · genomes 3/152,030 · joint denominator

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.Arg313Ser
Coding: c.937C>A
MANE Select: NM_003742
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

Disease context

familial intrahepatic cholestasis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: progressive familial intrahepatic cholestasis type 2

Similar variants

ABCB11 p.Arg313Leu Uncertain significance ★ ⚠ same residue
ABCB11 p.Arg313Cys Uncertain significance ★ ⚠ same residue
ABCB11 p.Arg313His Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCB11 p.Arg313= Likely benign ★ same residue
ABCB11 c.1084-2A>G Pathogenic ★★ same condition
ABCB11 c.1197+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-2A>C Likely 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/abcb11-p-arg313ser (accessed [today's date]).

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