Is ABCC9 p.Asn124= (c.372T>C) pathogenic?

ABCC9 p.Asn124= (c.372T>C) is classified Conflicting classifications of pathogenicity in ABCC9 (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-05-01). Ultra-rare (popmax 0.0955%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ABCC9 p.Asn124= (c.372T>C)?

ABCC9 p.Asn124= (c.372T>C) is associated with Cardiovascular phenotype, cardiomyopathy, hypertrichotic osteochondrodysplasia Cantu type (ClinVar).

How common is ABCC9 p.Asn124= (c.372T>C) in the general population?

ABCC9 p.Asn124= (c.372T>C) is ultra-rare (popmax 0.0955%, nfe) (gnomAD).

ABCC9 p.Asn124=

c.372T>C · rs377384557 · VCV45410

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0955%, 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 -1.6	GERP -3.7
Overall
CADD	2.309	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0955% European (non-Finnish) · 1,126/1,179,624 alleles

Filtering AF 0.0908% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0889%

Overall 0.0737% 1,190/1,613,634 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0955%	1,048
Middle Eastern	0.0329%	3,041
Finnishnot grpmax-eligible	0.0312%	3,201
Remaining individualsnot grpmax-eligible	0.0288%	3,471
Admixed American	0.0233%	4,286
African / African-American	0.012%	8,327
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Asn124=
Coding: c.372T>C
MANE Select: NM_020297
dbSNP: rs377384557
Type: single nucleotide variant
Location: chr12:21925976 (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

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

Also linked: cardiomyopathy hypertrichotic osteochondrodysplasia Cantu type dilated cardiomyopathy 1O

Similar variants

ABCC9 p.Asn124Lys 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.Gly989Glu 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-asn124 (accessed [today's date]).

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