Is PPIG p.Ser62Arg (c.186T>A) pathogenic?

PPIG p.Ser62Arg (c.186T>A) is classified Uncertain significance in PPIG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely pathogenic (0.9765); Absent from gnomAD v4.1.

How common is PPIG p.Ser62Arg (c.186T>A) in the general population?

PPIG p.Ser62Arg (c.186T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPIG p.Ser62Arg (c.186T>A)?

AlphaMissense predicts likely pathogenic (score 0.9765) — an in-silico prediction, not a clinical call.

PPIG p.Ser62Arg

c.186T>A · rs2468326495 · VCV3217208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9765 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9765	likely pathogenic
REVEL	0.284	benign-leaning
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 11 kb · p 1.8e-15 · regional, not allelic
Overall
CADD	24.1	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: PPIG
Protein: p.Ser62Arg
Coding: c.186T>A
MANE Select: NM_004792
dbSNP: rs2468326495
Type: single nucleotide variant
Location: chr2:169606088 (GRCh38)
Gene constraint: LOEUF 0.472 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.64 · 4 PDB
Residue 62: the ppiase cyclophilin-type domain

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

Similar variants

PPIG c.929+11A>G Benign ★★ same type
PPIG p.Asn672= Benign ★★ same type
PPIG p.Glu495= Benign ★★ same type
PPIG p.Thr54= Benign ★★ same type
PPIG p.Ala542Thr Uncertain significance ★ ⚠ same type
PPIG p.Arg235Gln Uncertain significance ★ ⚠ same type
PPIG p.Arg239Gln Uncertain significance ★ ⚠ same type
PPIG p.Arg350Lys 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/ppig-p-ser62arg (accessed [today's date]).

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