Is PRF1 p.Arg371Ter (c.1103_1110dup) pathogenic?

PRF1 p.Arg371Ter (c.11031110dup) is classified Pathogenic in PRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-25). Absent from gnomAD; Associated with familial hemophagocytic lymphohistiocytosis 2.

What condition is associated with PRF1 p.Arg371Ter (c.1103_1110dup)?

PRF1 p.Arg371Ter (c.1103_1110dup) is associated with familial hemophagocytic lymphohistiocytosis 2 (ClinVar).

How common is PRF1 p.Arg371Ter (c.1103_1110dup) in the general population?

PRF1 p.Arg371Ter (c.1103_1110dup) is absent from gnomAD (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PRF1 p.Arg371Ter

c.1103_1110dup · rs2132475735 · VCV1072304

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

familial hemophagocytic lymphohistiocytosis 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP 1.1, phastCons 0.98

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRF1
Protein: p.Arg371Ter
Coding: c.1103_1110dup
MANE Select: NM_001083116
dbSNP: rs2132475735
Type: Duplication
Location: chr10:70598610 (GRCh38)
Gene constraint: LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.01
Residue 371: a disulfide bond; the macpf domain

Full PRF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial hemophagocytic lymphohistiocytosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 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.Arg371= Likely benign ★ same residue
PRF1 p.Leu189fs Pathogenic/Likely pathogenic ★★ same condition
PRF1 p.Thr114delinsMetTer Likely pathogenic ★★ same condition
PRF1 p.Trp425fs Pathogenic ★★ same condition
PRF1 p.Cys23fs Pathogenic ★ same condition
PRF1 p.Pro477fs 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-arg371ter (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown