Is PPCS p.Phe96= (c.288C>T) pathogenic?

PPCS p.Phe96= (c.288C>T) is classified Likely benign in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-27). Rare (popmax 0.178%, afr).

How common is PPCS p.Phe96= (c.288C>T) in the general population?

PPCS p.Phe96= (c.288C>T) is rare (popmax 0.178%, afr) (gnomAD).

PPCS p.Phe96=

c.288C>T · rs188411740 · VCV1620875

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.178%, 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 1.8	GERP -0.73, phastCons 1
Overall
CADD	12.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.178% African / African-American · 134/75,078 alleles

Filtering AF 0.154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.145%

Overall 0.00936% 151/1,613,536 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.178%	560
Admixed American	0.0183%	5,458
Remaining individualsnot grpmax-eligible	0.0096%	10,418

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.Phe96=
Coding: c.288C>T
MANE Select: NM_001395517 · reported on NM_024664
dbSNP: rs188411740
Type: single nucleotide variant
Location: chr1:42456853 (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-phe96 (accessed [today's date]).

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