PRF1 p.Pro39Arg
c.116C>G · VCV4907753
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4897 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4897 | ambiguous |
|---|---|---|
| REVEL | 0.867 | moderately pathogenic-leaning |
| SaProt | LLR -9.62 | tolerated |
| ⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 2,846 bp · p 0.42 · regional, not allelic |
| Overall | ||
| CADD | 23.9 | 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
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PRF1
- Protein
- p.Pro39Arg
- Coding
- c.116C>G
- MANE Select
- NM_001083116
- Type
- single nucleotide variant
- Location
- chr10:70600787 (GRCh38)
- Gene constraint
- LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.01
- Residue 39
- the macpf domain
Similar variants
- PRF1 p.Pro39His Pathogenic/Likely pathogenic ★★ ⚠ same residue
- PRF1 p.Pro39= Likely benign ★ same residue
- PRF1 c.539+2T>A Pathogenic/Likely pathogenic ★★ same type
- PRF1 p.Arg225Trp Pathogenic ★★ ⚠ same type
- PRF1 p.Arg232Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- PRF1 p.Arg299Cys Pathogenic/Likely pathogenic ★★ same type
- PRF1 p.Arg356Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- PRF1 p.Arg361Trp Pathogenic/Likely pathogenic ★★ ⚠ 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/prf1-p-pro39arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown