Is PPID p.Ile98Val (c.292A>G) pathogenic?

PPID p.Ile98Val (c.292A>G) is classified Uncertain significance in PPID (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.1192); Very rare (popmax 8.5e-05%, nfe).

How common is PPID p.Ile98Val (c.292A>G) in the general population?

PPID p.Ile98Val (c.292A>G) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about PPID p.Ile98Val (c.292A>G)?

AlphaMissense predicts likely benign (score 0.1192) — an in-silico prediction, not a clinical call.

PPID p.Ile98Val

c.292A>G · VCV3782267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1192 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1192	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -10.75	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, 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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,470 alleles

Overall 6.21e-05% 1/1,609,850 alleles · very rare exomes 1/1,457,484 · genomes 0/152,366 · joint denominator

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.Ile98Val
Coding: c.292A>G
MANE Select: NM_005038
Type: single nucleotide variant
Location: chr4:158719221 (GRCh38)
Gene constraint: LOEUF 1.303 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.51
Residue 98: the ppiase cyclophilin-type domain

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-ile98val (accessed [today's date]).

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