Is ABCB4 p.Ser101Leu (c.302C>T) pathogenic?

ABCB4 p.Ser101Leu (c.302C>T) is classified Uncertain significance in ABCB4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-13). AlphaMissense: likely benign (0.1098); Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with ABCB4 p.Ser101Leu (c.302C>T)?

ABCB4 p.Ser101Leu (c.302C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB4 p.Ser101Leu (c.302C>T) in the general population?

ABCB4 p.Ser101Leu (c.302C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about ABCB4 p.Ser101Leu (c.302C>T)?

AlphaMissense predicts likely benign (score 0.1098) — an in-silico prediction, not a clinical call.

ABCB4 p.Ser101Leu

c.302C>T · rs182989205 · VCV598359

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1098 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1098	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.7	GERP 1, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 31 kb · p 4.4e-11 · regional, not allelic
Overall
CADD	20.1	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 0.0156% East Asian · 7/44,746 alleles

Filtering AF 0.00728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00516%

Overall 0.00211% 34/1,610,586 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,392
Admixed American	0.00501%	19,973
South Asian	0.00332%	30,141
African / African-American	0.00267%	37,448
Remaining individualsnot grpmax-eligible	0.0016%	62,376
European (non-Finnish)	0.00153%	65,434

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: ABCB4
Protein: p.Ser101Leu
Coding: c.302C>T
MANE Select: NM_000443
dbSNP: rs182989205
Type: single nucleotide variant
Location: chr7:87454577 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 101: the abc transmembrane type-1 1 domain

Full ABCB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCB4 p.Ser101= Conflicting classifications of pathogenicity ★ same residue
ABCB4 p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
ABCB4 p.Ala304Ser Uncertain significance ★★ ⚠ same condition
ABCB4 p.Ala333Thr Uncertain significance ★★ ⚠ same condition
ABCB4 p.Arg159Gln Uncertain significance ★★ ⚠ same condition
ABCB4 p.Arg661His Uncertain significance ★★ ⚠ same condition
ABCB4 p.Arg969Cys Uncertain significance ★★ ⚠ same condition
ABCB4 p.Cys1226Gly Uncertain significance ★★ ⚠ 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/abcb4-p-ser101leu (accessed [today's date]).

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