Is PSMC2 p.Arg360Cys (c.1078C>T) pathogenic?

PSMC2 p.Arg360Cys (c.1078C>T) is classified Uncertain significance in PSMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: ambiguous (0.39); Ultra-rare (popmax 0.0176%, sas).

How common is PSMC2 p.Arg360Cys (c.1078C>T) in the general population?

PSMC2 p.Arg360Cys (c.1078C>T) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

What do computational predictors say about PSMC2 p.Arg360Cys (c.1078C>T)?

AlphaMissense predicts ambiguous (score 0.39) — an in-silico prediction, not a clinical call.

PSMC2 p.Arg360Cys

c.1078C>T · VCV3426947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.39 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.39	ambiguous
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -14.38	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 445 bp · p 2.2e-07 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.0176% South Asian · 16/90,994 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00899%

Overall 0.00124% 20/1,613,842 alleles · ultra-rare exomes 20/1,461,640 · genomes 0/152,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,687
Admixed American	0.00167%	60,006
African / African-American	0.00133%	74,976
European (non-Finnish)	0.00017%	589,957

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: PSMC2
Protein: p.Arg360Cys
Coding: c.1078C>T
MANE Select: NM_002803
Type: single nucleotide variant
Location: chr7:103367743 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.73 · 139 PDB
Residue 360: a β-strand

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

Similar variants

PSMC2 p.Ala235Val Uncertain significance ★ ⚠ same type
PSMC2 p.Ala24Val Uncertain significance ★ ⚠ same type
PSMC2 p.Ala412Ser Uncertain significance ★ ⚠ same type
PSMC2 p.Ala7Ser Uncertain significance ★ ⚠ same type
PSMC2 p.Arg375Gln Uncertain significance ★ ⚠ same type
PSMC2 p.Asp347Glu Uncertain significance ★ ⚠ same type
PSMC2 p.Gln47His Uncertain significance ★ ⚠ same type
PSMC2 p.Glu14Ala 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/psmc2-p-arg360cys (accessed [today's date]).

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