Is PRF1 p.Ser234= (c.702G>A) pathogenic?

PRF1 p.Ser234= (c.702G>A) is classified Benign/Likely benign in PRF1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Low-frequency (popmax 2.77%, afr); Associated with lymphoma, non-Hodgkin, familial.

What condition is associated with PRF1 p.Ser234= (c.702G>A)?

PRF1 p.Ser234= (c.702G>A) is associated with lymphoma, non-Hodgkin, familial, familial hemophagocytic lymphohistiocytosis 2, autoinflammatory syndrome (ClinVar).

How common is PRF1 p.Ser234= (c.702G>A) in the general population?

PRF1 p.Ser234= (c.702G>A) is low-frequency (popmax 2.77%, afr) (gnomAD).

PRF1 p.Ser234=

c.702G>A · rs138508223 · VCV468309

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.77%, 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 -20	GERP -4.3
Overall
CADD	3.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.77% African / African-American · 2,076/75,048 alleles

Filtering AF 2.67% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.63%

Overall 0.142% 2,297/1,613,732 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.77%	36
Remaining individualsnot grpmax-eligible	0.163%	613
Admixed American	0.143%	698
Middle Eastern	0.099%	1,010
South Asian	0.0022%	45,535
European (non-Finnish)	0.00212%	47,188

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.Ser234=
Coding: c.702G>A
MANE Select: NM_001083116
dbSNP: rs138508223
Type: single nucleotide variant
Location: chr10:70599019 (GRCh38)
Gene constraint: LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.01
Residue 234: 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.Ser234Leu Uncertain significance ★★ ⚠ 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
PRF1 p.Arg390Ter 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-ser234 (accessed [today's date]).

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