Is PPCS p.Pro202= (c.606A>T) pathogenic?

PPCS p.Pro202= (c.606A>T) is classified Likely benign in PPCS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-25). Ultra-rare (popmax 0.084%, afr).

How common is PPCS p.Pro202= (c.606A>T) in the general population?

PPCS p.Pro202= (c.606A>T) is ultra-rare (popmax 0.084%, afr) (gnomAD).

PPCS p.Pro202=

c.606A>T · rs371461760 · VCV1585247

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.084%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.244	benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2	GERP 0.077, phastCons 1
Overall
CADD	12.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.084% African / African-American · 63/75,036 alleles

Filtering AF 0.0673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0613%

Overall 0.0049% 79/1,613,294 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.084%	1,191
Admixed American	0.0167%	6,003
Remaining individualsnot grpmax-eligible	0.0096%	10,412

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.Pro202=
Coding: c.606A>T
MANE Select: NM_001395517 · reported on NM_024664
dbSNP: rs371461760
Type: single nucleotide variant
Location: chr1:42457344 (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-pro202 (accessed [today's date]).

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