Is ABCC9 p.Cys515= (c.1545C>T) pathogenic?

ABCC9 p.Cys515= (c.1545C>T) is classified Likely benign in ABCC9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-06). Very rare (popmax 0.00161%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ABCC9 p.Cys515= (c.1545C>T)?

ABCC9 p.Cys515= (c.1545C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Cys515= (c.1545C>T) in the general population?

ABCC9 p.Cys515= (c.1545C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

ABCC9 p.Cys515=

c.1545C>T · rs760680023 · VCV1774918

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Conditions

Cardiovascular phenotype

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 4	GERP 1.9, phastCons 1
Overall
CADD	10.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,179,382 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00316% 51/1,612,984 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0438%	2,286
Remaining individualsnot grpmax-eligible	0.00641%	15,606
European (non-Finnish)grpmax	0.00161%	62,073

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys515=
Coding: c.1545C>T
MANE Select: NM_020297
dbSNP: rs760680023
Type: single nucleotide variant
Location: chr12:21906199 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72
Residue 515: the abc transmembrane type-1 1 domain

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1O

Similar variants

ABCC9 p.Cys515Ser Uncertain significance ★ ⚠ same residue
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

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-cys515 (accessed [today's date]).

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