PUS1 p.Pro414=
c.1242C>G · rs898900975 · VCV1140658
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00801%, afr)
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 -0.18 | GERP -2.5, phastCons 0.12 |
| Overall | ||
| CADD | 1.907 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00801%
African / African-American · 6/74,938 alleles
Filtering AF
0.00347%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00228%
Overall
0.000496%
8/1,613,362 alleles · very rare
exomes 3/1,461,106 · genomes 5/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00801% | 12,490 |
| Admixed American | 0.00167% | 60,008 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,456 |
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
- PUS1
- Protein
- p.Pro414=
- Coding
- c.1242C>G
- MANE Select
- NM_025215
- dbSNP
- rs898900975
- Type
- single nucleotide variant
- Location
- chr12:131943544 (GRCh38)
- Gene constraint
- LOEUF 1.161 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.80 · 6 PDB
- Residue 414
- a UniProt-annotated variant site (in mlasa1); the 'disordered' region
Similar variants
- PUS1 p.Pro414Ser Uncertain significance ★ same residue
- PUS1 p.Gln101Ter Pathogenic/Likely pathogenic ★★ same type
- PUS1 p.Gln154Ter Pathogenic ★★ same type
- PUS1 p.Lys306Ter Pathogenic/Likely pathogenic ★★ same type
- PUS1 p.Trp15Ter Pathogenic/Likely pathogenic ★★ same type
- PUS1 p.Trp161Ter Pathogenic/Likely pathogenic ★★ same type
- PUS1 p.Ala226Thr Uncertain significance ★★ ⚠ same type
- PUS1 p.Ala309Val 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/pus1-p-pro414 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown