Is PSME2 p.Val153= (c.459C>G) pathogenic?

PSME2 p.Val153= (c.459C>G) is classified Benign in PSME2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-11). Common (popmax 8.35%, afr) — too common for a highly-penetrant pathogenic allele.

PSME2 p.Val153=

Q: How common is PSME2 p.Val153= (c.459C>G) in the general population?

PSME2 p.Val153= (c.459C>G) is common (popmax 8.35%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.459C>G · rs17101478 · VCV768641

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.35%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -4.6, phastCons 1
Overall
CADD	4.931	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.35% African / African-American · 6,261/75,008 alleles

Filtering AF 8.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.1%

Overall 0.429% 6,918/1,614,164 alleles · common exomes 3,400/1,461,884 · genomes 3,518/152,280 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.35%	12
Remaining individualsnot grpmax-eligible	0.533%	188
Admixed American	0.398%	251
Middle Eastern	0.115%	866
South Asian	0.0329%	3,036
European (non-Finnish)	0.00398%	25,107
East Asian	0.00223%	44,884

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.Val153=
Coding: c.459C>G
MANE Select: NM_002818
dbSNP: rs17101478
Type: single nucleotide variant
Location: chr14:24144230 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 5 PDB
Residue 153: 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.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-val153 (accessed [today's date]).

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