Is ABCC9 p.Arg864Lys (c.2591G>A) pathogenic?

ABCC9 p.Arg864Lys (c.2591G>A) is classified Uncertain significance in ABCC9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-29). AlphaMissense: ambiguous (0.4396); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ABCC9 p.Arg864Lys (c.2591G>A)?

ABCC9 p.Arg864Lys (c.2591G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Arg864Lys (c.2591G>A) in the general population?

ABCC9 p.Arg864Lys (c.2591G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC9 p.Arg864Lys (c.2591G>A)?

AlphaMissense predicts ambiguous (score 0.4396) — an in-silico prediction, not a clinical call.

ABCC9 p.Arg864Lys

c.2591G>A · rs1592071215 · VCV656428

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4396 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4396	ambiguous
REVEL	0.605	indeterminate
SaProt	LLR -6.14	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 6,731 bp · p 0.0027 · regional, not allelic
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCC9
Protein: p.Arg864Lys
Coding: c.2591G>A
MANE Select: NM_020297
dbSNP: rs1592071215
Type: single nucleotide variant
Location: chr12:21852420 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72
Residue 864: the abc transporter 1 domain

Full ABCC9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1O

Similar variants

ABCC9 p.Arg864Ser Uncertain significance ★ ⚠ same residue
ABCC9 p.Arg864= Likely benign ★ same residue
ABCC9 p.Arg864fs Pathogenic ★ same residue
ABCC9 c.2506-1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC9 p.Arg1116Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCC9 p.Arg1116His Pathogenic ★★ ⚠ same condition
ABCC9 p.Arg1154Gln Pathogenic ★★ same condition
ABCC9 p.Arg1154Trp Pathogenic/Likely pathogenic ★★ same condition

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/abcc9-p-arg864lys (accessed [today's date]).

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