Is PRF1 p.Val111fs (c.327del) pathogenic?

PRF1 p.Val111fs (c.327del) is classified Pathogenic in PRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). No gnomAD frequency available for this variant; Associated with familial hemophagocytic lymphohistiocytosis 2.

What condition is associated with PRF1 p.Val111fs (c.327del)?

PRF1 p.Val111fs (c.327del) is associated with familial hemophagocytic lymphohistiocytosis 2 (ClinVar).

How common is PRF1 p.Val111fs (c.327del) in the general population?

PRF1 p.Val111fs (c.327del) is no gnomAD frequency available for this variant (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

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

PRF1 p.Val111fs

c.327del · rs2493487405 · VCV2852100

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.28	GERP -1.5

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.Val111fs
Coding: c.327del
MANE Select: NM_001083116
dbSNP: rs2493487405
Type: Deletion
Location: chr10:70600576 (GRCh38)
Gene constraint: LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.01
Residue 111: 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.Asp484fs Pathogenic ★★ same condition
PRF1 p.Asp62fs Pathogenic ★★ same condition
PRF1 p.Cys73fs Pathogenic ★★ same condition
PRF1 p.Glu323fs Pathogenic/Likely pathogenic ★★ same condition
PRF1 p.His308fs Pathogenic/Likely pathogenic ★★ same condition
PRF1 p.Leu17fs Pathogenic ★★ same condition
PRF1 p.Leu360fs Pathogenic/Likely pathogenic ★★ same condition
PRF1 p.Leu364fs 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-val111fs (accessed [today's date]).

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