Is PPCS p.Thr68Pro (c.202A>C) pathogenic?

PPCS p.Thr68Pro (c.202A>C) is classified Uncertain significance in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.3095); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PPCS p.Thr68Pro (c.202A>C)?

PPCS p.Thr68Pro (c.202A>C) is associated with Inborn genetic diseases (ClinVar).

How common is PPCS p.Thr68Pro (c.202A>C) in the general population?

PPCS p.Thr68Pro (c.202A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPCS p.Thr68Pro (c.202A>C)?

AlphaMissense predicts likely benign (score 0.3095) — an in-silico prediction, not a clinical call.

PPCS p.Thr68Pro

c.202A>C · rs776659652 · VCV2615388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3095 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3095	likely benign
REVEL	0.327	indeterminate
SaProt	LLR -11.27	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.008	GERP -4.3
Regional constraint	o/e 1.04	unconstrained · MANE · 687 bp · p 0.55 · regional, not allelic
Overall
CADD	10.51	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPCS
Protein: p.Thr68Pro
Coding: c.202A>C
MANE Select: NM_024664
dbSNP: rs776659652
Type: single nucleotide variant
Location: chr1:42456767 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.94 · 2 PDB
Residue 68: an α-helix

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

Similar variants

PPCS p.Ala162Pro Uncertain significance ★★ ⚠ same condition
PPCS p.Pro107Ser Uncertain significance ★★ ⚠ same condition
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 c.508+14G>C Likely benign ★ 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-thr68pro (accessed [today's date]).

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