Is PPID p.Pro10Ser (c.28C>T) pathogenic?

PPID p.Pro10Ser (c.28C>T) is classified Uncertain significance in PPID (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.1412); Very rare (popmax 8.47e-05%, nfe).

How common is PPID p.Pro10Ser (c.28C>T) in the general population?

PPID p.Pro10Ser (c.28C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PPID p.Pro10Ser (c.28C>T)?

AlphaMissense predicts likely benign (score 0.1412) — an in-silico prediction, not a clinical call.

PPID p.Pro10Ser

c.28C>T · VCV4142407

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1412 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1412	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -4.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.49 · regional, not allelic
Overall
CADD	24.0	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 8.47e-05% European (non-Finnish) · 1/1,180,008 alleles

Overall 6.84e-05% 1/1,461,684 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: PPID
Protein: p.Pro10Ser
Coding: c.28C>T
MANE Select: NM_005038
Type: single nucleotide variant
Location: chr4:158723261 (GRCh38)
Gene constraint: LOEUF 1.303 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.51

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

Similar variants

PPID p.Val177Ile Benign ★★ same type
PPID p.Ala299Pro Uncertain significance ★ ⚠ same type
PPID p.Ala326Thr Uncertain significance ★ ⚠ same type
PPID p.Ala356Thr Uncertain significance ★ ⚠ same type
PPID p.Arg125His Uncertain significance ★ ⚠ same type
PPID p.Arg312Cys Uncertain significance ★ ⚠ same type
PPID p.Arg312His Uncertain significance ★ same type
PPID p.Arg31Gln 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/ppid-p-pro10ser (accessed [today's date]).

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