Is ABCC9 p.Arg281Pro (c.842G>C) pathogenic?

ABCC9 p.Arg281Pro (c.842G>C) is classified Uncertain significance in ABCC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-28). AlphaMissense: ambiguous (0.4045); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ABCC9 p.Arg281Pro (c.842G>C)?

ABCC9 p.Arg281Pro (c.842G>C) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCC9 p.Arg281Pro (c.842G>C) in the general population?

ABCC9 p.Arg281Pro (c.842G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC9 p.Arg281Pro (c.842G>C)?

AlphaMissense predicts ambiguous (score 0.4045) — an in-silico prediction, not a clinical call.

ABCC9 p.Arg281Pro

c.842G>C · VCV4861379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4045 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,597,380)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4045	ambiguous
REVEL	0.357	indeterminate
SaProt	LLR -9.66	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -0.32, phastCons 0.003
Regional constraint	o/e 0.53	unconstrained · MANE · 29 kb · p 4.3e-29 · regional, not allelic
Overall
CADD	19.54	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 1,597,380). 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: ABCC9
Protein: p.Arg281Pro
Coding: c.842G>C
MANE Select: NM_020297
Type: single nucleotide variant
Location: chr12:21913041 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72

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

Similar variants

ABCC9 p.Arg281Gln Uncertain significance ★★ ⚠ same residue
ABCC9 p.Arg281Trp Uncertain significance ★ ⚠ same residue
ABCC9 c.2092+5G>T Uncertain significance ★★ same condition
ABCC9 c.3893-3C>T Uncertain significance ★★ same condition
ABCC9 c.4512+693G>A Uncertain significance ★★ ⚠ same condition
ABCC9 c.4512+733C>A Uncertain significance ★★ ⚠ same condition
ABCC9 p.Ala136Ser Uncertain significance ★★ same condition
ABCC9 p.Ala276Thr Uncertain significance ★★ ⚠ 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-arg281pro (accessed [today's date]).

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