Is PPID p.Ser198Pro (c.592T>C) pathogenic?

PPID p.Ser198Pro (c.592T>C) is classified Uncertain significance in PPID (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely benign (0.3378); Very rare (popmax 0.00333%, amr).

How common is PPID p.Ser198Pro (c.592T>C) in the general population?

PPID p.Ser198Pro (c.592T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about PPID p.Ser198Pro (c.592T>C)?

AlphaMissense predicts likely benign (score 0.3378) — an in-silico prediction, not a clinical call.

PPID p.Ser198Pro

c.592T>C · VCV3423521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3378 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3378	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -13.86	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.49 · regional, not allelic
Overall
CADD	22.5	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

Grpmax group 0.00333% Admixed American · 2/60,032 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.00093% 15/1,613,540 alleles · very rare exomes 15/1,461,192 · genomes 0/152,348 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,016
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.00102%	98,288

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.Ser198Pro
Coding: c.592T>C
MANE Select: NM_005038
Type: single nucleotide variant
Location: chr4:158715615 (GRCh38)
Gene constraint: LOEUF 1.303 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.51
Residue 198: a modified residue (phosphoserine); the 'chaperone activity' region

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-ser198pro (accessed [today's date]).

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