Is ABCC9 p.Ile381Val (c.1141A>G) pathogenic?

ABCC9 p.Ile381Val (c.1141A>G) is classified Uncertain significance in ABCC9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-16). AlphaMissense: likely benign (0.3242); Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ABCC9 p.Ile381Val (c.1141A>G)?

ABCC9 p.Ile381Val (c.1141A>G) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Ile381Val (c.1141A>G) in the general population?

ABCC9 p.Ile381Val (c.1141A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ABCC9 p.Ile381Val (c.1141A>G)?

AlphaMissense predicts likely benign (score 0.3242) — an in-silico prediction, not a clinical call.

ABCC9 p.Ile381Val

c.1141A>G · rs2137875072 · VCV3017597

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3242 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3242	likely benign
REVEL	0.526	indeterminate
SaProt	LLR -4.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 29 kb · p 4.3e-29 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00133% African / African-American · 1/74,964 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,612,406 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,964
European (non-Finnish)	0.00017%	589,341

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: ABCC9
Protein: p.Ile381Val
Coding: c.1141A>G
MANE Select: NM_020297
dbSNP: rs2137875072
Type: single nucleotide variant
Location: chr12:21910849 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72
Residue 381: the abc transmembrane type-1 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.Ile381Asn Uncertain significance ★★ ⚠ same residue
ABCC9 p.Ile381Thr Uncertain significance ★ ⚠ same residue
ABCC9 p.Ile381= Likely benign ★ 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-ile381val (accessed [today's date]).

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