Is ABCB9 p.Leu689Pro (c.2066T>C) pathogenic?

ABCB9 p.Leu689Pro (c.2066T>C) is classified Uncertain significance in ABCB9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: ambiguous (0.4208); Absent from gnomAD v4.1.

How common is ABCB9 p.Leu689Pro (c.2066T>C) in the general population?

ABCB9 p.Leu689Pro (c.2066T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB9 p.Leu689Pro (c.2066T>C)?

AlphaMissense predicts ambiguous (score 0.4208) — an in-silico prediction, not a clinical call.

ABCB9 p.Leu689Pro

c.2066T>C · VCV4636108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4208 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,550,874)

Computational evidence

Protein change
AlphaMissense	0.4208	ambiguous
REVEL	0.642	indeterminate
SaProt	LLR -7.00	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP -2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 30 kb · p 0.00058 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,550,874). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCB9
Protein: p.Leu689Pro
Coding: c.2066T>C
MANE Select: NM_019625
Type: single nucleotide variant
Location: chr12:122930146 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.76
Residue 689: the abc transporter domain

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

Similar variants

ABCB9 p.Leu689= 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-leu689pro (accessed [today's date]).

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