Is ABCB9 p.Leu299Val (c.895C>G) pathogenic?

ABCB9 p.Leu299Val (c.895C>G) is classified Uncertain significance in ABCB9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely benign (0.2172); Very rare (popmax 0.00169%, amr).

How common is ABCB9 p.Leu299Val (c.895C>G) in the general population?

ABCB9 p.Leu299Val (c.895C>G) is very rare (popmax 0.00169%, amr) (gnomAD).

What do computational predictors say about ABCB9 p.Leu299Val (c.895C>G)?

AlphaMissense predicts likely benign (score 0.2172) — an in-silico prediction, not a clinical call.

ABCB9 p.Leu299Val

c.895C>G · VCV3867609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2172 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2172	likely benign
REVEL	0.269	benign-leaning
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.16, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 30 kb · p 0.00058 · regional, not allelic
Overall
CADD	19.77	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 0.00169% Admixed American · 1/59,270 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000412% 6/1,454,584 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00169%	59,270
Remaining individualsnot grpmax-eligible	0.00161%	62,154
South Asian	0.00111%	90,364
European (non-Finnish)	0.000255%	392,091

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: ABCB9
Protein: p.Leu299Val
Coding: c.895C>G
MANE Select: NM_019625
Type: single nucleotide variant
Location: chr12:122948782 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.76
Residue 299: the abc transmembrane type-1 domain

Full ABCB9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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ABCB9 p.Ala368Val Uncertain significance ★ ⚠ same type
ABCB9 p.Ala447Thr Uncertain significance ★ ⚠ same type
ABCB9 p.Ala641Ser Uncertain significance ★ ⚠ same type
ABCB9 p.Ala641Thr Uncertain significance ★ ⚠ same type
ABCB9 p.Ala64Thr Uncertain significance ★ ⚠ same type

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/abcb9-p-leu299val (accessed [today's date]).

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