Is PPCS p.Glu233Val (c.698A>T) pathogenic?

PPCS p.Glu233Val (c.698A>T) is classified Pathogenic/Likely pathogenic in PPCS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-03). AlphaMissense: likely pathogenic (0.946); Absent from gnomAD v4.1; Associated with cardiomyopathy, dilated, 2c.

What condition is associated with PPCS p.Glu233Val (c.698A>T)?

PPCS p.Glu233Val (c.698A>T) is associated with cardiomyopathy, dilated, 2c (ClinVar).

How common is PPCS p.Glu233Val (c.698A>T) in the general population?

PPCS p.Glu233Val (c.698A>T) is absent from gnomAD v4.1 (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PPCS p.Glu233Val (c.698A>T)?

AlphaMissense predicts likely pathogenic (score 0.946) — an in-silico prediction, not a clinical call.

PPCS p.Glu233Val

c.698A>T · rs1557778277 · VCV590782

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.946 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cardiomyopathy, dilated, 2c

Computational evidence

Protein change
AlphaMissense	0.946	likely pathogenic ✓ concordant with ClinVar
REVEL	0.723	pathogenic-leaning
SaProt	LLR -13.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 2,669 bp · p 5.9e-05 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPCS
Protein: p.Glu233Val
Coding: c.698A>T
MANE Select: NM_024664
dbSNP: rs1557778277
Type: single nucleotide variant
Location: chr1:42459688 (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-glu233val (accessed [today's date]).

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