Is PPCS p.Gly288= (c.864C>T) pathogenic?

PPCS p.Gly288= (c.864C>T) is classified Likely benign in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). Very rare (popmax 0.00934%, afr).

How common is PPCS p.Gly288= (c.864C>T) in the general population?

PPCS p.Gly288= (c.864C>T) is very rare (popmax 0.00934%, afr) (gnomAD).

PPCS p.Gly288=

c.864C>T · rs146331223 · VCV1506127

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

⚠ 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 -0.22	GERP -4.6
Overall
CADD	9.439	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,966 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000805% 13/1,613,960 alleles · very rare exomes 8/1,461,840 · genomes 5/152,120 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,709
East Asian	0.00892%	11,216
European (non-Finnish)	0.000169%	589,988

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.Gly288=
Coding: c.864C>T
MANE Select: NM_024664
dbSNP: rs146331223
Type: single nucleotide variant
Location: chr1:42459854 (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-gly288 (accessed [today's date]).

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