Is PPCS p.Pro236Ser (c.706C>T) pathogenic?

PPCS p.Pro236Ser (c.706C>T) is classified Uncertain significance in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: likely benign (0.1168); Ultra-rare (popmax 0.0117%, amr).

How common is PPCS p.Pro236Ser (c.706C>T) in the general population?

PPCS p.Pro236Ser (c.706C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about PPCS p.Pro236Ser (c.706C>T)?

AlphaMissense predicts likely benign (score 0.1168) — an in-silico prediction, not a clinical call.

PPCS p.Pro236Ser

c.706C>T · rs781102134 · VCV1406900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1168 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1168	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -9.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 2,669 bp · p 5.9e-05 · regional, not allelic
Overall
CADD	20.9	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 0.0117% Admixed American · 7/59,998 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000434% 7/1,613,964 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.Pro236Ser
Coding: c.706C>T
MANE Select: NM_001395517 · reported on NM_024664
dbSNP: rs781102134
Type: single nucleotide variant
Location: chr1:42459696 (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-pro236ser (accessed [today's date]).

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