Is PPCS p.Val254= (c.762G>C) pathogenic?

PPCS p.Val254= (c.762G>C) is classified Benign in PPCS (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-27). Rare (popmax 0.822%, sas).

How common is PPCS p.Val254= (c.762G>C) in the general population?

PPCS p.Val254= (c.762G>C) is rare (popmax 0.822%, sas) (gnomAD).

PPCS p.Val254=

c.762G>C · rs146107417 · VCV1572621

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.822%, sas)

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.6	GERP -0.76, phastCons 1
Overall
CADD	7.629	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.822% South Asian · 749/91,088 alleles

Filtering AF 0.773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.754%

Overall 0.0817% 1,318/1,614,174 alleles · rare exomes 1,233/1,461,874 · genomes 85/152,300 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.822%	122
Middle Eastern	0.66%	151
Ashkenazi Jewishnot grpmax-eligible	0.409%	245
Remaining individualsnot grpmax-eligible	0.131%	762
Admixed American	0.0333%	3,001
European (non-Finnish)	0.0256%	3,907
African / African-American	0.00533%	18,759

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.Val254=
Coding: c.762G>C
MANE Select: NM_024664
dbSNP: rs146107417
Type: single nucleotide variant
Location: chr1:42459752 (GRCh38)

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

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-val254 (accessed [today's date]).

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