Is ABCB9 p.Ala729= (c.2187C>T) pathogenic?

ABCB9 p.Ala729= (c.2187C>T) is classified Likely benign in ABCB9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). Very rare (popmax 0.000431%, nfe).

How common is ABCB9 p.Ala729= (c.2187C>T) in the general population?

ABCB9 p.Ala729= (c.2187C>T) is very rare (popmax 0.000431%, nfe) (gnomAD).

ABCB9 p.Ala729=

c.2187C>T · VCV3868418

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000431%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -5.3, phastCons 0.12
Overall
CADD	5.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000431% European (non-Finnish) · 5/1,161,078 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.2e-05%

Overall 0.000318% 5/1,573,930 alleles · very rare

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.Ala729=
Coding: c.2187C>T
MANE Select: NM_019625
Type: single nucleotide variant
Location: chr12:122930025 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.76
Residue 729: the abc transporter domain

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

Similar variants

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
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-ala729 (accessed [today's date]).

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