Is ABCC9 p.Leu362fs (c.1084_1085del) pathogenic?

ABCC9 p.Leu362fs (c.10841085del) is classified Conflicting classifications of pathogenicity in ABCC9 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-22). Very rare (popmax 8.48e-05%, nfe); Associated with dilated cardiomyopathy 1O.

What condition is associated with ABCC9 p.Leu362fs (c.1084_1085del)?

ABCC9 p.Leu362fs (c.1084_1085del) is associated with dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Leu362fs (c.1084_1085del) in the general population?

ABCC9 p.Leu362fs (c.1084_1085del) 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.Leu362fs

c.1084_1085del · VCV4804857

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

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 9 of 40
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.085	GERP -3.7, phastCons 0.012
Overall
CADD	34.0	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) · 1/1,178,956 alleles

Overall 0.000658% 1/151,914 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.Leu362fs
Coding: c.1084_1085del
MANE Select: NM_020297
Type: Microsatellite
Location: chr12:21910905 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72
Residue 362: the abc transmembrane type-1 1 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.Ala292fs Uncertain significance ★★ same condition
ABCC9 p.Asn14del Uncertain significance ★★ same condition
ABCC9 p.Arg808fs Pathogenic ★ same condition
ABCC9 c.1619-9_1619-6del Uncertain significance ★ same condition
ABCC9 c.2339+8_2339+9insACAGAGGTAATTTTTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCC Uncertain significance ★ same condition
ABCC9 c.817-14_817-4del Conflicting classifications of pathogenicity ★ same condition
ABCC9 c.1165-20_1165-19del Likely benign ★ same condition
ABCC9 c.1659+15CT[2] 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-leu362fs (accessed [today's date]).

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