Is ABCB9 p.Arg717Cys (c.2149C>T) pathogenic?

ABCB9 p.Arg717Cys (c.2149C>T) is classified Uncertain significance in ABCB9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-24). AlphaMissense: likely benign (0.0858); Very rare (popmax 0.0051%, nfe).

How common is ABCB9 p.Arg717Cys (c.2149C>T) in the general population?

ABCB9 p.Arg717Cys (c.2149C>T) is very rare (popmax 0.0051%, nfe) (gnomAD).

What do computational predictors say about ABCB9 p.Arg717Cys (c.2149C>T)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

ABCB9 p.Arg717Cys

c.2149C>T · VCV3979064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0051%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.401	indeterminate
SaProt	LLR -7.99	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 7.4	GERP -2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 30 kb · p 0.00058 · regional, not allelic
Overall
CADD	23.0	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 0.0051% European (non-Finnish) · 59/1,156,792 alleles

Filtering AF 0.00402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00368%

Overall 0.00402% 63/1,567,716 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0051%	19,607
Remaining individualsnot grpmax-eligible	0.00329%	30,382
Admixed American	0.0019%	52,606
South Asian	0.00117%	85,328

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.Arg717Cys
Coding: c.2149C>T
MANE Select: NM_019625
Type: single nucleotide variant
Location: chr12:122930063 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.76
Residue 717: the abc transporter domain

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

Similar variants

ABCB9 p.Arg717His Uncertain significance ★ ⚠ same residue
ABCB9 p.Arg717= 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

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-arg717cys (accessed [today's date]).

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