Is ABCC9 p.Tyr352= (c.1056C>T) pathogenic?

ABCC9 p.Tyr352= (c.1056C>T) is classified Benign/Likely benign in ABCC9 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-03). Rare (popmax 0.871%, afr); Associated with dilated cardiomyopathy 1O.

What condition is associated with ABCC9 p.Tyr352= (c.1056C>T)?

ABCC9 p.Tyr352= (c.1056C>T) is associated with dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Tyr352= (c.1056C>T) in the general population?

ABCC9 p.Tyr352= (c.1056C>T) is rare (popmax 0.871%, afr) (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.Tyr352=

c.1056C>T · rs149408382 · VCV45380

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.871%, afr)

Conditions

dilated cardiomyopathy 1O

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.46	GERP -3.7
Overall
CADD	3.786	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.871% African / African-American · 653/74,944 alleles

Filtering AF 0.816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.794%

Overall 0.0471% 759/1,612,404 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.871%	115
Middle Eastern	0.0661%	1,514
Admixed American	0.0652%	1,535
Remaining individualsnot grpmax-eligible	0.0545%	1,836
European (non-Finnish)	0.00238%	42,100
South Asian	0.0011%	91,040

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.Tyr352=
Coding: c.1056C>T
MANE Select: NM_020297
dbSNP: rs149408382
Type: single nucleotide variant
Location: chr12:21910934 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72
Residue 352: 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 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
ABCC9 p.Gln852Ter Pathogenic/Likely pathogenic ★★ same condition
ABCC9 p.Thr1202Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCC9 p.Val1266Met 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-tyr352 (accessed [today's date]).

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