Is ABCC9 p.Ile995fs (c.2982del) pathogenic?

ABCC9 p.Ile995fs (c.2982del) is classified Pathogenic in ABCC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). Very rare (popmax 8.48e-05%, nfe); Associated with dilated cardiomyopathy 1O.

What condition is associated with ABCC9 p.Ile995fs (c.2982del)?

ABCC9 p.Ile995fs (c.2982del) is associated with dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Ile995fs (c.2982del) in the general population?

ABCC9 p.Ile995fs (c.2982del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCC9 p.Ile995fs

c.2982del · VCV3671535

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

dilated cardiomyopathy 1O

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 26 of 40
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP -2.3, phastCons 1
Overall
CADD	29.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,850 alleles

Overall 0.000657% 1/152,170 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: ABCC9
Protein: p.Ile995fs
Coding: c.2982del
MANE Select: NM_020297
Type: Deletion
Location: chr12:21845717 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72
Residue 995: the abc transmembrane type-1 2 domain

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

Disease context

dilated cardiomyopathy 1O — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ABCC9 p.Ile995Val Uncertain significance ★★ ⚠ same residue
ABCC9 p.Gly1339fs Uncertain significance ★★ same condition
ABCC9 c.1012-14del Likely benign ★★ same condition
ABCC9 c.1165-20del Likely benign ★★ same condition
ABCC9 c.1165-6del Benign ★★ same condition
ABCC9 c.1456-10del Likely benign ★★ same condition
ABCC9 c.2238-17del Benign ★★ same condition
ABCC9 c.3567-19_3567-13del Likely benign ★★ 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-ile995fs (accessed [today's date]).

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