Is PPCS p.Arg65= (c.195C>T) pathogenic?

PPCS p.Arg65= (c.195C>T) is classified Likely benign in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). Very rare (popmax 0.00533%, afr).

How common is PPCS p.Arg65= (c.195C>T) in the general population?

PPCS p.Arg65= (c.195C>T) is very rare (popmax 0.00533%, afr) (gnomAD).

PPCS p.Arg65=

c.195C>T · VCV3608036

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

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 0.13	GERP -0.88, phastCons 0.93
Overall
CADD	11.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 4/75,056 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00062% 10/1,611,960 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,764
Remaining individualsnot grpmax-eligible	0.0016%	62,460
European (non-Finnish)	0.000424%	235,937

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.Arg65=
Coding: c.195C>T
MANE Select: NM_001395517 · reported on NM_024664
Type: single nucleotide variant
Location: chr1:42456760 (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-arg65 (accessed [today's date]).

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