PRF1 p.Arg371=
c.1113G>A · rs2132475717 · VCV1552598
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
familial hemophagocytic lymphohistiocytosis 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 1.2, phastCons 0.77 |
| Overall | ||
| CADD | 7.639 | PHRED · no single calibrated threshold — expert panels disagree |
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.Arg371=
- Coding
- c.1113G>A
- MANE Select
- NM_001083116
- dbSNP
- rs2132475717
- Type
- single nucleotide variant
- Location
- chr10:70598608 (GRCh38)
- Gene constraint
- LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.01
- Residue 371
- the macpf domain
Disease context
familial hemophagocytic lymphohistiocytosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Familial hemophagocytic lymphohistiocytosis (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Infancy
- Prevalence
- 1-9 / 100 000 (Sweden)
Similar variants
- PRF1 p.Arg371Gly Uncertain significance ★★ ⚠ same residue
- PRF1 p.Arg371Lys Uncertain significance ★★ ⚠ same residue
- PRF1 p.Arg371Ter Pathogenic ★ same residue
- PRF1 c.539+2T>A Pathogenic/Likely pathogenic ★★ same condition
- PRF1 p.Arg225Trp Pathogenic ★★ ⚠ same condition
- PRF1 p.Arg232Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PRF1 p.Arg299Cys Pathogenic/Likely pathogenic ★★ same condition
- PRF1 p.Arg356Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
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-arg371 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown