Is PSMD2 p.Ile109Val (c.325A>G) pathogenic?

PSMD2 p.Ile109Val (c.325A>G) is classified Uncertain significance in PSMD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). AlphaMissense: likely benign (0.142); Very rare (popmax 8.47e-05%, nfe).

How common is PSMD2 p.Ile109Val (c.325A>G) in the general population?

PSMD2 p.Ile109Val (c.325A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PSMD2 p.Ile109Val (c.325A>G)?

AlphaMissense predicts likely benign (score 0.142) — an in-silico prediction, not a clinical call.

PSMD2 p.Ile109Val

c.325A>G · rs2473948004 · VCV2551698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.142 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.142	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 0.71, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,320 bp · p 0.31 · regional, not allelic
Overall
CADD	19.05	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,978 alleles

Overall 6.2e-05% 1/1,614,146 alleles · very rare exomes 1/1,461,804 · genomes 0/152,342 · 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: PSMD2
Protein: p.Ile109Val
Coding: c.325A>G
MANE Select: NM_002808
dbSNP: rs2473948004
Type: single nucleotide variant
Location: chr3:184300412 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.98 · 129 PDB
Residue 109: a turn

Full PSMD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PSMD2 p.Ala197Ser Uncertain significance ★ ⚠ same type
PSMD2 p.Ala227Thr Uncertain significance ★ ⚠ same type
PSMD2 p.Ala269Thr Uncertain significance ★ ⚠ same type
PSMD2 p.Ala412Ser Uncertain significance ★ ⚠ same type
PSMD2 p.Ala642Thr Uncertain significance ★ ⚠ same type
PSMD2 p.Ala644Thr Uncertain significance ★ ⚠ same type
PSMD2 p.Ala648Gly Uncertain significance ★ ⚠ same type
PSMD2 p.Ala880Thr 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/psmd2-p-ile109val (accessed [today's date]).

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