PSMC4 p.Ala75=
c.225C>T · VCV3426961
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.89 | phastCons 0.002 |
| Overall | ||
| CADD | 10.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,010 alleles
Overall
6.2e-05%
1/1,614,058 alleles · very rare
exomes 1/1,461,864 · genomes 0/152,194 · 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
- PSMC4
- Protein
- p.Ala75=
- Coding
- c.225C>T
- MANE Select
- NM_006503
- Type
- single nucleotide variant
- Location
- chr19:39972458 (GRCh38)
- Gene constraint
- LOEUF 0.407 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.33 · 140 PDB
- Residue 75
- an α-helix
Similar variants
- PSMC4 p.Arg178Gln Uncertain significance ★ ⚠ same type
- PSMC4 p.Arg252His Uncertain significance ★ ⚠ same type
- PSMC4 p.Arg43His Uncertain significance ★ ⚠ same type
- PSMC4 p.Asp13His Uncertain significance ★ ⚠ same type
- PSMC4 p.Asp161Gly Uncertain significance ★ same type
- PSMC4 p.Asp197Asn Uncertain significance ★ ⚠ same type
- PSMC4 p.Gln24His Uncertain significance ★ ⚠ same type
- PSMC4 p.Glu33Lys 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/psmc4-p-ala75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown