Is ABCB11 p.Pro970Ser (c.2908C>T) pathogenic?

ABCB11 p.Pro970Ser (c.2908C>T) is classified Conflicting classifications of pathogenicity in ABCB11 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-03). AlphaMissense: likely benign (0.1607); Rare (popmax 0.127%, amr).

How common is ABCB11 p.Pro970Ser (c.2908C>T) in the general population?

ABCB11 p.Pro970Ser (c.2908C>T) is rare (popmax 0.127%, amr) (gnomAD).

What do computational predictors say about ABCB11 p.Pro970Ser (c.2908C>T)?

AlphaMissense predicts likely benign (score 0.1607) — an in-silico prediction, not a clinical call.

ABCB11 p.Pro970Ser

c.2908C>T · rs779096015 · VCV593179

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1607 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.127%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1607	likely benign
REVEL	0.397	indeterminate
SaProt	LLR -9.94	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 5.6	GERP 1, phastCons 1
Overall
CADD	17.46	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 0.127% Admixed American · 76/60,006 alleles

Filtering AF 0.104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0953%

Overall 0.0049% 79/1,613,870 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.127%	790
Remaining individualsnot grpmax-eligible	0.0032%	31,231
European (non-Finnish)	8.48e-05%	1,179,903

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.Pro970Ser
Coding: c.2908C>T
MANE Select: NM_003742
dbSNP: rs779096015
Type: single nucleotide variant
Location: chr2:168935332 (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 970: an α-helix; the abc transmembrane type-1 2 domain

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

Similar variants

ABCB11 p.Pro970= 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
ABCB11 c.1435-2A>T Pathogenic/Likely pathogenic ★★ same type
ABCB11 c.150+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCB11 c.150+2T>C 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/abcb11-p-pro970ser (accessed [today's date]).

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