Is PRF1 p.Phe37= (c.111C>T) pathogenic?

PRF1 p.Phe37= (c.111C>T) is classified Conflicting classifications of pathogenicity in PRF1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.47%, sas); Associated with autoinflammatory syndrome.

What condition is associated with PRF1 p.Phe37= (c.111C>T)?

PRF1 p.Phe37= (c.111C>T) is associated with autoinflammatory syndrome, familial hemophagocytic lymphohistiocytosis 2 (ClinVar).

How common is PRF1 p.Phe37= (c.111C>T) in the general population?

PRF1 p.Phe37= (c.111C>T) is low-frequency (popmax 1.47%, sas) (gnomAD).

PRF1 p.Phe37=

c.111C>T · rs547321451 · VCV785783

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.47%, sas)

Conditions

autoinflammatory syndrome

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 -11	GERP -4
Overall
CADD	0.043	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.47% South Asian · 1,331/90,842 alleles

Filtering AF 1.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.37%

Overall 0.0873% 1,406/1,610,878 alleles · low-frequency exomes 1,328/1,458,540 · genomes 78/152,338 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.47%	68
Middle Eastern	0.116%	861
Remaining individualsnot grpmax-eligible	0.0738%	1,354
East Asian	0.00447%	22,394
African / African-American	0.00267%	37,513
European (non-Finnish)	0.00153%	65,436

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: PRF1
Protein: p.Phe37=
Coding: c.111C>T
MANE Select: NM_001083116
dbSNP: rs547321451
Type: single nucleotide variant
Location: chr10:70600792 (GRCh38)
Gene constraint: LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.01
Residue 37: the macpf domain

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

Disease context

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hemophagocytic lymphohistiocytosis 2

Similar variants

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
PRF1 p.Arg361Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRF1 p.Arg390Ter Pathogenic ★★ same condition
PRF1 p.Arg410Pro 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-phe37 (accessed [today's date]).

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