Is PPCS p.Pro236= (c.708C>T) pathogenic?

PPCS p.Pro236= (c.708C>T) is classified Benign/Likely benign in PPCS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Rare (popmax 0.3%, sas).

How common is PPCS p.Pro236= (c.708C>T) in the general population?

PPCS p.Pro236= (c.708C>T) is rare (popmax 0.3%, sas) (gnomAD).

PPCS p.Pro236=

c.708C>T · rs575586967 · VCV2187338

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.3%, sas)

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 -2.4	GERP -4.6
Overall
CADD	4.573	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.3% South Asian · 273/91,076 alleles

Filtering AF 0.271% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.259%

Overall 0.0191% 308/1,614,146 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.3%	334
Remaining individualsnot grpmax-eligible	0.0208%	4,808
European (non-Finnish)	0.00178%	56,191
Admixed American	0.00167%	60,024

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.Pro236=
Coding: c.708C>T
MANE Select: NM_001395517 · reported on NM_024664
dbSNP: rs575586967
Type: single nucleotide variant
Location: chr1:42459698 (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-pro236 (accessed [today's date]).

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