Is ABCB11 p.Met677Val (c.2029A>G) pathogenic?

ABCB11 p.Met677Val (c.2029A>G) is classified Benign/Likely benign in ABCB11 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-04-14). AlphaMissense: likely benign (0.0538); Common (popmax 17.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Met677Val (c.2029A>G)?

ABCB11 p.Met677Val (c.2029A>G) is associated with familial intrahepatic cholestasis, progressive familial intrahepatic cholestasis type 2 (ClinVar).

What do computational predictors say about ABCB11 p.Met677Val (c.2029A>G)?

AlphaMissense predicts likely benign (score 0.0538) — an in-silico prediction, not a clinical call.

ABCB11 p.Met677Val

Q: How common is ABCB11 p.Met677Val (c.2029A>G) in the general population?

ABCB11 p.Met677Val (c.2029A>G) is common (popmax 17.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2029A>G · rs11568364 · VCV259145

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0538 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 17.1%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
AlphaMissense	0.0538	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -5.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	donor gain · deltas
Constraint at this position
Conservation	phyloP -0.056	GERP -4.2
Overall
CADD	0.352	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 17.1% African / African-American · 12,796/74,856 alleles

Filtering AF 16.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.7%

Overall 2.35% 37,834/1,611,012 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	17.1%	6
Middle Eastern	4.42%	23
Remaining individualsnot grpmax-eligible	2.72%	37
Admixed American	2.18%	46
European (non-Finnish)	1.7%	59
Ashkenazi Jewishnot grpmax-eligible	1.4%	71
South Asian	1.18%	85
Finnishnot grpmax-eligible	0.336%	297

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.Met677Val
Coding: c.2029A>G
MANE Select: NM_003742
dbSNP: rs11568364
Type: single nucleotide variant
Location: chr2:168968473 (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 677: a UniProt-annotated variant site (does not affect taurocholate transport activity; does not affect protein expression; does not affect cell surface protein expression)

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 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
ABCB11 c.1435-2A>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+3A>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1638+1G>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-met677val (accessed [today's date]).

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