Is PRF1 p.Asp484fs (c.1451del) pathogenic?

PRF1 p.Asp484fs (c.1451del) is classified Pathogenic in PRF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-09). Very rare (popmax 0.000678%, nfe); Associated with aplastic anemia.

What condition is associated with PRF1 p.Asp484fs (c.1451del)?

PRF1 p.Asp484fs (c.1451del) is associated with aplastic anemia, familial hemophagocytic lymphohistiocytosis 2 (ClinVar).

How common is PRF1 p.Asp484fs (c.1451del) in the general population?

PRF1 p.Asp484fs (c.1451del) is very rare (popmax 0.000678%, nfe) (gnomAD).

PRF1 p.Asp484fs

c.1451del · rs755693770 · VCV2735409

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

aplastic anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	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	GERP -4.2

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,032 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,614,202 alleles · very rare exomes 8/1,461,894 · genomes 0/152,308 · joint denominator

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.Asp484fs
Coding: c.1451del
MANE Select: NM_001083116
dbSNP: rs755693770
Type: Deletion
Location: chr10:70598270 (GRCh38)
Gene constraint: LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.01
Residue 484: a binding site; the c2 domain

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

Disease context

aplastic anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hemophagocytic lymphohistiocytosis 2

Similar variants

PRF1 p.Asp484Asn Uncertain significance ★ ⚠ same residue
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-asp484fs (accessed [today's date]).

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