Is ABCB11 p.Tyr93= (c.279C>T) pathogenic?

ABCB11 p.Tyr93= (c.279C>T) is classified Conflicting classifications of pathogenicity in ABCB11 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-04-14). Ultra-rare (popmax 0.0691%, eas); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Tyr93= (c.279C>T)?

ABCB11 p.Tyr93= (c.279C>T) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Tyr93= (c.279C>T) in the general population?

ABCB11 p.Tyr93= (c.279C>T) is ultra-rare (popmax 0.0691%, eas) (gnomAD).

ABCB11 p.Tyr93=

c.279C>T · rs375137002 · VCV383625

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0691%, eas)

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.065	GERP -3.5, phastCons 0.007
Overall
CADD	0.877	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0691% East Asian · 31/44,870 alleles

Filtering AF 0.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0435%

Overall 0.00886% 143/1,613,764 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0691%	1,447
Remaining individualsnot grpmax-eligible	0.0176%	5,680
Finnishnot grpmax-eligible	0.0156%	6,402
South Asian	0.00878%	11,383
European (non-Finnish)	0.00687%	14,565
Admixed American	0.00333%	29,995

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.Tyr93=
Coding: c.279C>T
MANE Select: NM_003742
dbSNP: rs375137002
Type: single nucleotide variant
Location: chr2:169013382 (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 93: the abc transmembrane type-1 1 domain; an α-helix

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

Similar variants

ABCB11 p.Tyr93Ter Pathogenic ★★ same residue
ABCB11 p.Tyr93Ser Uncertain significance ★ ⚠ 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.1435-2A>T 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-tyr93 (accessed [today's date]).

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