Is PRF1 p.Asp62fs (c.185_195del) pathogenic?

PRF1 p.Asp62fs (c.185195del) is classified Pathogenic in PRF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-05). Very rare (popmax 8.48e-05%, nfe); Associated with aplastic anemia.

What condition is associated with PRF1 p.Asp62fs (c.185_195del)?

PRF1 p.Asp62fs (c.185_195del) is associated with aplastic anemia, familial hemophagocytic lymphohistiocytosis 2 (ClinVar).

How common is PRF1 p.Asp62fs (c.185_195del) in the general population?

PRF1 p.Asp62fs (c.185_195del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

PRF1 p.Asp62fs

c.185_195del · rs774071705 · VCV1069593

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, 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	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 1, phastCons 0.97

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,884 alleles

Overall 0.000186% 3/1,613,668 alleles · very rare exomes 3/1,461,554 · genomes 0/152,114 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,494
Finnishnot grpmax-eligible	0.00156%	63,906
European (non-Finnish)grpmax	8.48e-05%	1,179,884

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp62fs
Coding: c.185_195del
MANE Select: NM_001083116
dbSNP: rs774071705
Type: Deletion
Location: chr10:70600708 (GRCh38)
Gene constraint: LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.01
Residue 62: the macpf 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.Asp484fs 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
PRF1 p.Lys284_Lys287del 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-asp62fs (accessed [today's date]).

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