Is ABCB11 p.Arg299Ser (c.897A>T) pathogenic?

ABCB11 p.Arg299Ser (c.897A>T) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.2936); Ultra-rare (popmax 0.0667%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCB11 p.Arg299Ser (c.897A>T)?

ABCB11 p.Arg299Ser (c.897A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB11 p.Arg299Ser (c.897A>T) in the general population?

ABCB11 p.Arg299Ser (c.897A>T) is ultra-rare (popmax 0.0667%, afr) (gnomAD).

What do computational predictors say about ABCB11 p.Arg299Ser (c.897A>T)?

AlphaMissense predicts likely benign (score 0.2936) — an in-silico prediction, not a clinical call.

ABCB11 p.Arg299Ser

c.897A>T · VCV4099847

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2936 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0667%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2936	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -9.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP -1.7, phastCons 1
Overall
CADD	21.5	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 0.0667% African / African-American · 50/74,968 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0467%

Overall 0.0036% 58/1,613,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0667%	1,499
Remaining individualsnot grpmax-eligible	0.00801%	12,484
Admixed American	0.005%	19,981

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.Arg299Ser
Coding: c.897A>T
MANE Select: NM_003742
Type: single nucleotide variant
Location: chr2:168990812 (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 299: an α-helix; the abc transmembrane type-1 1 domain; a UniProt-annotated variant site (in)

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.Arg299Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCB11 p.Ala1283Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Ala693Thr Uncertain significance ★★ ⚠ same condition
ABCB11 p.Arg299Ile Uncertain significance ★★ same residue
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

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-arg299ser (accessed [today's date]).

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