Is PPCS p.Ser134= (c.402C>T) pathogenic?

PPCS p.Ser134= (c.402C>T) is classified Likely benign in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). Ultra-rare (popmax 0.034%, sas).

How common is PPCS p.Ser134= (c.402C>T) in the general population?

PPCS p.Ser134= (c.402C>T) is ultra-rare (popmax 0.034%, sas) (gnomAD).

PPCS p.Ser134=

c.402C>T · VCV3717826

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.6	GERP 1.1, phastCons 1
Overall
CADD	7.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.034% South Asian · 31/91,092 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00214% 31/1,451,716 alleles · ultra-rare

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.Ser134=
Coding: c.402C>T
MANE Select: NM_024664
Type: single nucleotide variant
Location: chr1:42456967 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.94 · 2 PDB
Residue 134: an α-helix

Full PPCS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPCS p.Ala162Pro Uncertain significance ★★ ⚠ same type
PPCS p.Pro107Ser Uncertain significance ★★ ⚠ same type
PPCS c.*91T>G Benign ★★ same type
PPCS p.Leu280= Benign/Likely benign ★★ same type
PPCS p.Phe73= Likely benign ★★ same type
PPCS p.Ala8Ser Uncertain significance ★ ⚠ same type
PPCS p.Leu118Met Uncertain significance ★ ⚠ same type
PPCS p.Thr68Pro Uncertain significance ★ ⚠ same type

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-ser134 (accessed [today's date]).

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