PSMC5 p.Ile254=
c.762C>T · VCV4936541
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0172%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.54 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.8 | GERP -4.8 |
| Overall | ||
| CADD | 4.932 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0172%
Middle Eastern · 1/5,830 alleles
Filtering AF
0.00168%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00145%
Overall
0.0023%
36/1,567,318 alleles · ultra-rare
exomes 33/1,415,160 · genomes 3/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0172% | 5,830 |
| Remaining individualsnot grpmax-eligible | 0.00497% | 20,123 |
| Admixed American | 0.00364% | 27,495 |
| European (non-Finnish) | 0.00242% | 41,284 |
| South Asian | 0.00241% | 41,477 |
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
- PSMC5
- Protein
- p.Ile254=
- Coding
- c.762C>T
- MANE Select
- NM_002805
- Type
- single nucleotide variant
- Location
- chr17:63831118 (GRCh38)
- Gene constraint
- LOEUF 0.386 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 82.47 · 140 PDB
- Residue 254
- the 'may mediate interaction with prpf9' region; a turn
Similar variants
- PSMC5 p.Pro320Arg Pathogenic/Likely pathogenic ★★ same type
- PSMC5 c.264+9A>G Benign ★★ same type
- PSMC5 c.97-8T>C Benign ★★ same type
- PSMC5 p.Leu219= Benign ★★ same type
- PSMC5 p.Leu280= Benign ★★ same type
- PSMC5 p.Arg325Trp Pathogenic ★ same type
- PSMC5 p.Met368Thr Likely pathogenic ★ ⚠ same type
- PSMC5 c.1081-2A>G 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/psmc5-p-ile254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown