Is PSMC3IP p.Arg108Pro (c.323G>C) pathogenic?

PSMC3IP p.Arg108Pro (c.323G>C) is classified Uncertain significance in PSMC3IP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely pathogenic (0.8117); Absent from gnomAD v4.1.

How common is PSMC3IP p.Arg108Pro (c.323G>C) in the general population?

PSMC3IP p.Arg108Pro (c.323G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PSMC3IP p.Arg108Pro (c.323G>C)?

AlphaMissense predicts likely pathogenic (score 0.8117) — an in-silico prediction, not a clinical call.

PSMC3IP p.Arg108Pro

c.323G>C · VCV4573296

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8117 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8117	likely pathogenic · top 10% in PSMC3IP
REVEL	0.257	benign-leaning
SaProt	LLR -14.25	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 4,715 bp · p 0.42 · regional, not allelic
Overall
CADD	33.0	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

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: PSMC3IP
Protein: p.Arg108Pro
Coding: c.323G>C
MANE Select: NM_016556
Type: single nucleotide variant
Location: chr17:42574113 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.45

Full PSMC3IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PSMC3IP p.Arg108His Likely benign ★★ same residue
PSMC3IP p.Glu160Lys Uncertain significance ★★ ⚠ same type
PSMC3IP c.136-10C>T Benign ★★ same type
PSMC3IP c.225+79G>A Benign ★★ same type
PSMC3IP c.225+89C>T Likely benign ★★ same type
PSMC3IP c.337+88C>T Benign ★★ same type
PSMC3IP c.338-147T>C Benign ★★ same type
PSMC3IP c.338-158G>A Benign ★★ 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/psmc3ip-p-arg108pro (accessed [today's date]).

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