Is ABCC9 p.Lys923fs (c.2768del) pathogenic?

ABCC9 p.Lys923fs (c.2768del) is classified Conflicting classifications of pathogenicity in ABCC9 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-22). Very rare (popmax 0.00134%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ABCC9 p.Lys923fs (c.2768del)?

ABCC9 p.Lys923fs (c.2768del) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Lys923fs (c.2768del) in the general population?

ABCC9 p.Lys923fs (c.2768del) is very rare (popmax 0.00134%, afr) (gnomAD).

ABCC9 p.Lys923fs

c.2768del · rs775677708 · VCV1394160

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Cardiovascular phenotype

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 24 of 40
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
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 0.00134% African / African-American · 1/74,854 alleles

Overall 0.000658% 1/152,056 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.Lys923fs
Coding: c.2768del
MANE Select: NM_020297
dbSNP: rs775677708
Type: Deletion
Location: chr12:21852098 (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: dilated cardiomyopathy 1O

Similar variants

ABCC9 p.Gly1339fs Uncertain significance ★★ same condition
ABCC9 c.1012-14del Likely benign ★★ same condition
ABCC9 c.1165-20del Likely benign ★★ same condition
ABCC9 c.1165-6del Benign ★★ same condition
ABCC9 c.1456-10del Likely benign ★★ same condition
ABCC9 c.2238-17del Benign ★★ same condition
ABCC9 c.3567-19_3567-13del Likely benign ★★ same condition
ABCC9 c.4103-15del 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-lys923fs (accessed [today's date]).

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