Is PPCS p.Leu213fs (c.636_639del) pathogenic?

PPCS p.Leu213fs (c.636639del) is classified Likely pathogenic in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-30). Ultra-rare (popmax 0.0434%, afr); Associated with cardiomyopathy, dilated, 2c.

What condition is associated with PPCS p.Leu213fs (c.636_639del)?

PPCS p.Leu213fs (c.636_639del) is associated with cardiomyopathy, dilated, 2c (ClinVar).

How common is PPCS p.Leu213fs (c.636_639del) in the general population?

PPCS p.Leu213fs (c.636_639del) is ultra-rare (popmax 0.0434%, 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.

PPCS p.Leu213fs

c.636_639del · rs912203499 · VCV1679771

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0434%, afr)

Conditions

cardiomyopathy, dilated, 2c

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.4	GERP -3.1
Overall
CADD	5.625	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 0.0434% African / African-American · 28/64,474 alleles

Filtering AF 0.0308% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0266%

Overall 0.00244% 30/1,229,652 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0434%	2,303
Admixed American	0.00422%	23,682
Remaining individualsnot grpmax-eligible	0.00219%	45,656

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: PPCS
Protein: p.Leu213fs
Coding: c.636_639del
MANE Select: NM_001395517 · reported on NM_001287511
dbSNP: rs912203499
Type: Deletion
Location: chr1:42473144 (GRCh38)

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

Disease context

cardiomyopathy, dilated, 2c — 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)

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/ppcs-p-leu213fs (accessed [today's date]).

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