Is PSMC2 p.Pro109Ser (c.325C>T) pathogenic?

PSMC2 p.Pro109Ser (c.325C>T) is classified Uncertain significance in PSMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). AlphaMissense: likely benign (0.1329); Absent from gnomAD v4.1.

How common is PSMC2 p.Pro109Ser (c.325C>T) in the general population?

PSMC2 p.Pro109Ser (c.325C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PSMC2 p.Pro109Ser (c.325C>T)?

AlphaMissense predicts likely benign (score 0.1329) — an in-silico prediction, not a clinical call.

PSMC2 p.Pro109Ser

c.325C>T · rs1820441024 · VCV2572203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1329 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1329	likely benign
REVEL	0.399	indeterminate
SaProt	LLR -9.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 9,254 bp · p 5.8e-16 · regional, not allelic
Overall
CADD	22.7	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

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: PSMC2
Protein: p.Pro109Ser
Coding: c.325C>T
MANE Select: NM_002803
dbSNP: rs1820441024
Type: single nucleotide variant
Location: chr7:103361991 (GRCh38)

Full PSMC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/psmc2-p-pro109ser (accessed [today's date]).

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