PUS7 p.Ser135=
c.405C>T · VCV3910634
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0112%, eas)
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 -2.3 | GERP -1.4 |
| Overall | ||
| CADD | 9.212 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0112%
East Asian · 5/44,810 alleles
Filtering AF
0.00435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00162%
26/1,608,888 alleles · ultra-rare
exomes 22/1,456,810 · genomes 4/152,078 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0112% | 8,962 |
| Admixed American | 0.00168% | 59,542 |
| European (non-Finnish) | 0.00161% | 61,935 |
| South Asian | 0.00111% | 90,240 |
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
- PUS7
- Protein
- p.Ser135=
- Coding
- c.405C>T
- MANE Select
- NM_019042
- Type
- single nucleotide variant
- Location
- chr7:105506267 (GRCh38)
- Gene constraint
- LOEUF 0.727 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.67 · 1 PDB
- Residue 135
- an α-helix
Similar variants
- PUS7 p.Ser135Ala Uncertain significance ★★ ⚠ same residue
- PUS7 c.1399-1G>C Pathogenic/Likely pathogenic ★★ same type
- PUS7 p.Asp503Tyr Pathogenic/Likely pathogenic ★★ same type
- PUS7 p.Arg661His Uncertain significance ★★ ⚠ same type
- PUS7 p.Met104Val Uncertain significance ★★ ⚠ same type
- PUS7 p.Thr269Ala Uncertain significance ★★ ⚠ same type
- PUS7 c.585+43G>C Benign ★★ same type
- PUS7 c.842+44A>G 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/pus7-p-ser135 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown