Is ABCB9 p.Ala698Val (c.2093C>T) pathogenic?

ABCB9 p.Ala698Val (c.2093C>T) is classified Uncertain significance in ABCB9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely pathogenic (0.9529); Very rare (popmax 0.00485%, eas).

How common is ABCB9 p.Ala698Val (c.2093C>T) in the general population?

ABCB9 p.Ala698Val (c.2093C>T) is very rare (popmax 0.00485%, eas) (gnomAD).

What do computational predictors say about ABCB9 p.Ala698Val (c.2093C>T)?

AlphaMissense predicts likely pathogenic (score 0.9529) — an in-silico prediction, not a clinical call.

ABCB9 p.Ala698Val

c.2093C>T · rs1275195096 · VCV3126937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9529 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00485%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9529	likely pathogenic
REVEL	0.719	pathogenic-leaning
SaProt	LLR -14.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 30 kb · p 0.00058 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00485% East Asian · 2/41,242 alleles

Filtering AF 0.000804% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000301%

Overall 0.00045% 7/1,554,896 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00485%	20,621
European (non-Finnish)	0.000435%	229,843

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.Ala698Val
Coding: c.2093C>T
MANE Select: NM_019625
dbSNP: rs1275195096
Type: single nucleotide variant
Location: chr12:122930119 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.76
Residue 698: the abc transporter domain

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

Similar variants

ABCB9 p.Ala698= 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-ala698val (accessed [today's date]).

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