Is ABCC9 p.Val220fs (c.654_657dup) pathogenic?

ABCC9 p.Val220fs (c.654657dup) is classified Pathogenic in ABCC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). Associated with dilated cardiomyopathy 1O.

What condition is associated with ABCC9 p.Val220fs (c.654_657dup)?

ABCC9 p.Val220fs (c.654_657dup) is associated with dilated cardiomyopathy 1O (ClinVar).

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.Val220fs

c.654_657dup · VCV4716285

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 7 of 40
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1, phastCons 1

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

Variant & gene context

Gene: ABCC9
Protein: p.Val220fs
Coding: c.654_657dup
MANE Select: NM_020297
Type: Duplication
Location: chr12:21915826 (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

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.Phe359_Leu360insTerPhe Pathogenic ★★ same condition
ABCC9 c.142+15dup Benign/Likely benign ★★ same condition
ABCC9 c.1803-5dup Benign/Likely benign ★★ same condition
ABCC9 c.2238-17dup Benign/Likely benign ★★ same condition
ABCC9 c.3097-19dup Benign/Likely benign ★★ same condition
ABCC9 c.817-16dup Benign/Likely benign ★★ same condition
ABCC9 c.817-18dup Benign/Likely benign ★★ same condition
ABCC9 p.Glu1273fs 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-val220fs (accessed [today's date]).

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