Is PPID p.Arg31Gln (c.92G>A) pathogenic?

PPID p.Arg31Gln (c.92G>A) is classified Uncertain significance in PPID (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: likely benign (0.2209); Very rare (popmax 0.000593%, nfe).

How common is PPID p.Arg31Gln (c.92G>A) in the general population?

PPID p.Arg31Gln (c.92G>A) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about PPID p.Arg31Gln (c.92G>A)?

AlphaMissense predicts likely benign (score 0.2209) — an in-silico prediction, not a clinical call.

PPID p.Arg31Gln

c.92G>A · rs746957379 · VCV2477351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2209 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2209	likely benign
REVEL	0.391	indeterminate
SaProt	LLR -14.52	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.79 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.49 · regional, not allelic
Overall
CADD	26.3	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 0.000593% European (non-Finnish) · 7/1,179,594 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,612,494 alleles · very rare exomes 5/1,460,462 · genomes 2/152,032 · 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.Arg31Gln
Coding: c.92G>A
MANE Select: NM_005038
dbSNP: rs746957379
Type: single nucleotide variant
Location: chr4:158721477 (GRCh38)
Gene constraint: LOEUF 1.303 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.51
Residue 31: 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.Arg49His 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-arg31gln (accessed [today's date]).

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