Is PPCS p.Thr151Ser (c.452C>G) pathogenic?

PPCS p.Thr151Ser (c.452C>G) is classified Uncertain significance in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.094); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PPCS p.Thr151Ser (c.452C>G)?

PPCS p.Thr151Ser (c.452C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PPCS p.Thr151Ser (c.452C>G) in the general population?

PPCS p.Thr151Ser (c.452C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about PPCS p.Thr151Ser (c.452C>G)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

PPCS p.Thr151Ser

c.452C>G · VCV4142223

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.454	indeterminate
SaProt	LLR -6.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 687 bp · p 0.55 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,832 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00025% 4/1,601,722 alleles · very 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.Thr151Ser
Coding: c.452C>G
MANE Select: NM_001395517 · reported on NM_024664
Type: single nucleotide variant
Location: chr1:42457017 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-thr151ser (accessed [today's date]).

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