Is PPCS p.Gln264His (c.792G>C) pathogenic?

PPCS p.Gln264His (c.792G>C) is classified Conflicting classifications of pathogenicity in PPCS (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1166); Rare (popmax 0.646%, afr); Associated with Cardiovascular phenotype.

What condition is associated with PPCS p.Gln264His (c.792G>C)?

PPCS p.Gln264His (c.792G>C) is associated with Cardiovascular phenotype, cardiomyopathy, dilated, 2c (ClinVar).

How common is PPCS p.Gln264His (c.792G>C) in the general population?

PPCS p.Gln264His (c.792G>C) is rare (popmax 0.646%, afr) (gnomAD).

What do computational predictors say about PPCS p.Gln264His (c.792G>C)?

AlphaMissense predicts likely benign (score 0.1166) — an in-silico prediction, not a clinical call.

PPCS p.Gln264His

c.792G>C · rs61745591 · VCV1028836

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1166 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.646%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1166	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -4.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.58	GERP -4.5, phastCons 0.99
Regional constraint	o/e 0.69	unconstrained · MANE · 2,669 bp · p 5.9e-05 · regional, not allelic
Overall
CADD	15.21	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

Grpmax group 0.646% African / African-American · 485/75,046 alleles

Filtering AF 0.599% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.58%

Overall 0.033% 533/1,614,192 alleles · rare exomes 241/1,461,862 · genomes 292/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.646%	155
Remaining individualsnot grpmax-eligible	0.0384%	2,605
Middle Eastern	0.033%	3,030
Admixed American	0.0267%	3,752
European (non-Finnish)	0.000508%	196,671

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.Gln264His
Coding: c.792G>C
MANE Select: NM_024664
dbSNP: rs61745591
Type: single nucleotide variant
Location: chr1:42459782 (GRCh38)

Full PPCS 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, dilated, 2c

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-gln264his (accessed [today's date]).

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