Is ABCB11 p.Phe236Ser (c.707T>C) pathogenic?

ABCB11 p.Phe236Ser (c.707T>C) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely benign (0.1016); Ultra-rare (popmax 0.0101%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCB11 p.Phe236Ser (c.707T>C)?

ABCB11 p.Phe236Ser (c.707T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB11 p.Phe236Ser (c.707T>C) in the general population?

ABCB11 p.Phe236Ser (c.707T>C) is ultra-rare (popmax 0.0101%, amr) (gnomAD).

What do computational predictors say about ABCB11 p.Phe236Ser (c.707T>C)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

ABCB11 p.Phe236Ser

c.707T>C · rs1001470159 · VCV3120789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -6.20	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.2	GERP -4, phastCons 0.99
Overall
CADD	19.11	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 0.0101% Admixed American · 6/59,686 alleles

Filtering AF 0.0043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.000559% 9/1,611,180 alleles · ultra-rare exomes 3/1,459,082 · genomes 6/152,098 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0101%	9,948
African / African-American	0.00267%	37,421
Remaining individualsnot grpmax-eligible	0.0016%	62,312

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.Phe236Ser
Coding: c.707T>C
MANE Select: NM_003742
dbSNP: rs1001470159
Type: single nucleotide variant
Location: chr2:168993787 (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 236: the abc transmembrane type-1 1 domain

Full ABCB11 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

ABCB11 p.Ala1283Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Ala693Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Asp1236Tyr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Cys1117Tyr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Glu395Asp Uncertain significance ★★ ⚠ same condition
ABCB11 p.Leu581Val Uncertain significance ★★ ⚠ same condition
ABCB11 p.Leu644Pro Uncertain significance ★★ ⚠ same condition
ABCB11 p.Lys1045Glu 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/abcb11-p-phe236ser (accessed [today's date]).

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