Is ABCC9 p.Arg191= (c.573G>A) pathogenic?

ABCC9 p.Arg191= (c.573G>A) is classified Uncertain significance in ABCC9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-03). Very rare (popmax 6.86e-05%); Associated with dilated cardiomyopathy 1O.

What condition is associated with ABCC9 p.Arg191= (c.573G>A)?

ABCC9 p.Arg191= (c.573G>A) is associated with dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Arg191= (c.573G>A) in the general population?

ABCC9 p.Arg191= (c.573G>A) is very rare (popmax 6.86e-05%) (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.Arg191=

c.573G>A · rs1948622763 · VCV3014472

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 6.86e-05%)

Conditions

dilated cardiomyopathy 1O

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	donor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.59	GERP -3.7, phastCons 0.054
Overall
CADD	11.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.86e-05%

Overall 6.86e-05% 1/1,457,944 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.Arg191=
Coding: c.573G>A
MANE Select: NM_020297
dbSNP: rs1948622763
Type: single nucleotide variant
Location: chr12:21916937 (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 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-arg191 (accessed [today's date]).

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