Is ABCB9 p.Arg2Trp (c.4C>T) pathogenic?

ABCB9 p.Arg2Trp (c.4C>T) is classified Uncertain significance in ABCB9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely benign (0.1434); Ultra-rare (popmax 0.0853%, afr).

How common is ABCB9 p.Arg2Trp (c.4C>T) in the general population?

ABCB9 p.Arg2Trp (c.4C>T) is ultra-rare (popmax 0.0853%, afr) (gnomAD).

What do computational predictors say about ABCB9 p.Arg2Trp (c.4C>T)?

AlphaMissense predicts likely benign (score 0.1434) — an in-silico prediction, not a clinical call.

ABCB9 p.Arg2Trp

c.4C>T · rs149734521 · VCV2244956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1434 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0853%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1434	likely benign
REVEL	0.448	indeterminate
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.039, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 30 kb · p 0.00058 · regional, not allelic
Overall
CADD	24.2	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 0.0853% African / African-American · 64/75,002 alleles

Filtering AF 0.0686% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0624%

Overall 0.0183% 294/1,609,940 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0853%	1,172
European (non-Finnish)	0.018%	5,554
Middle Eastern	0.0165%	6,050
Admixed American	0.0133%	7,491
Remaining individualsnot grpmax-eligible	0.0112%	8,911
South Asian	0.0022%	45,418

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.Arg2Trp
Coding: c.4C>T
MANE Select: NM_019625
dbSNP: rs149734521
Type: single nucleotide variant
Location: chr12:122960232 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.76

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

Similar variants

ABCB9 p.Arg2Gln Likely benign ★ same residue
ABCB9 p.Ala151Val Uncertain significance ★ ⚠ same type
ABCB9 p.Ala169Thr Uncertain significance ★ ⚠ same type
ABCB9 p.Ala364Val Uncertain significance ★ ⚠ same type
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

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-arg2trp (accessed [today's date]).

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