Is PSME2 p.Pro63Gln (c.188C>A) pathogenic?

PSME2 p.Pro63Gln (c.188C>A) is classified Uncertain significance in PSME2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-21). AlphaMissense: likely benign (0.1506); Ultra-rare (popmax 0.0218%, afr).

How common is PSME2 p.Pro63Gln (c.188C>A) in the general population?

PSME2 p.Pro63Gln (c.188C>A) is ultra-rare (popmax 0.0218%, afr) (gnomAD).

What do computational predictors say about PSME2 p.Pro63Gln (c.188C>A)?

AlphaMissense predicts likely benign (score 0.1506) — an in-silico prediction, not a clinical call.

PSME2 p.Pro63Gln

c.188C>A · rs369767757 · VCV2601867

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1506 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0218%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1506	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -10.11	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 7.6	GERP 2.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,165 bp · p 0.76 · regional, not allelic
Overall
CADD	24.4	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 0.0218% African / African-American · 16/73,230 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.00109% 17/1,562,072 alleles · ultra-rare exomes 6/1,409,886 · genomes 11/152,186 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0218%	4,577
Remaining individualsnot grpmax-eligible	0.00166%	60,196

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: PSME2
Protein: p.Pro63Gln
Coding: c.188C>A
MANE Select: NM_002818
dbSNP: rs369767757
Type: single nucleotide variant
Location: chr14:24145422 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 5 PDB
Residue 63: an α-helix

Full PSME2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PSME2 p.Pro67= Benign ★★ same type
PSME2 p.Val153= Benign ★★ same type
PSME2 p.Ala176Asp Uncertain significance ★ ⚠ same type
PSME2 p.Ala211Ser Uncertain significance ★ ⚠ same type
PSME2 p.Ala62Asp Uncertain significance ★ ⚠ same type
PSME2 p.Arg171Cys Uncertain significance ★ ⚠ same type
PSME2 p.Arg171His Uncertain significance ★ ⚠ same type
PSME2 p.Arg188Gln 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/psme2-p-pro63gln (accessed [today's date]).

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