Is PRF1 p.Cys242= (c.726C>T) pathogenic?

PRF1 p.Cys242= (c.726C>T) is classified Benign/Likely benign in PRF1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Low-frequency (popmax 3.95%, afr); Associated with lymphoma, non-Hodgkin, familial.

What condition is associated with PRF1 p.Cys242= (c.726C>T)?

PRF1 p.Cys242= (c.726C>T) is associated with lymphoma, non-Hodgkin, familial, familial hemophagocytic lymphohistiocytosis 2, autoinflammatory syndrome (ClinVar).

How common is PRF1 p.Cys242= (c.726C>T) in the general population?

PRF1 p.Cys242= (c.726C>T) is low-frequency (popmax 3.95%, afr) (gnomAD).

PRF1 p.Cys242=

c.726C>T · rs35329429 · VCV257406

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.95%, afr)

Conditions

lymphoma, non-Hodgkin, familial

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 -0.66	GERP -4.3
Overall
CADD	4.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.95% African / African-American · 2,962/75,048 alleles

Filtering AF 3.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.78%

Overall 0.23% 3,709/1,614,158 alleles · low-frequency exomes 1,927/1,461,824 · genomes 1,782/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.95%	25
Admixed American	0.411%	243
Remaining individualsnot grpmax-eligible	0.328%	305
Middle Eastern	0.281%	356
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,467
European (non-Finnish)	0.0214%	4,683
South Asian	0.0143%	7,006
East Asian	0.00223%	44,888

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.Cys242=
Coding: c.726C>T
MANE Select: NM_001083116
dbSNP: rs35329429
Type: single nucleotide variant
Location: chr10:70598995 (GRCh38)
Gene constraint: LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.01
Residue 242: a disulfide bond; the macpf domain

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

Disease context

lymphoma, non-Hodgkin, familial — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hemophagocytic lymphohistiocytosis 2 autoinflammatory syndrome

Similar variants

PRF1 p.Cys242Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
PRF1 p.Cys242Ter Likely 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
PRF1 p.Arg361Trp 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-cys242 (accessed [today's date]).

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