Is PSME2 p.Pro67= (c.201C>T) pathogenic?

PSME2 p.Pro67= (c.201C>T) is classified Benign in PSME2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-02). Common (popmax 6.2%, afr) — too common for a highly-penetrant pathogenic allele.

PSME2 p.Pro67=

Q: How common is PSME2 p.Pro67= (c.201C>T) in the general population?

PSME2 p.Pro67= (c.201C>T) is common (popmax 6.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.201C>T · rs61737105 · VCV781128

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.2%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.015	GERP -5.9, phastCons 0.15
Overall
CADD	8.126	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2% African / African-American · 4,586/73,940 alleles

Filtering AF 6.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.99%

Overall 0.336% 5,304/1,577,352 alleles · common exomes 2,710/1,425,084 · genomes 2,594/152,268 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.2%	16
Middle Eastern	0.564%	177
Admixed American	0.476%	210
Remaining individualsnot grpmax-eligible	0.43%	232
South Asian	0.019%	5,255
European (non-Finnish)	0.012%	8,300

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.Pro67=
Coding: c.201C>T
MANE Select: NM_002818
dbSNP: rs61737105
Type: single nucleotide variant
Location: chr14:24145409 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 5 PDB

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

Similar variants

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
PSME2 p.Arg188Gly 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-pro67 (accessed [today's date]).

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