Is PRF1 p.Ser170Arg (c.508A>C) pathogenic?

PRF1 p.Ser170Arg (c.508A>C) is classified Uncertain significance in PRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-19). AlphaMissense: ambiguous (0.4796); Very rare (popmax 0.000254%, nfe).

How common is PRF1 p.Ser170Arg (c.508A>C) in the general population?

PRF1 p.Ser170Arg (c.508A>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about PRF1 p.Ser170Arg (c.508A>C)?

AlphaMissense predicts ambiguous (score 0.4796) — an in-silico prediction, not a clinical call.

PRF1 p.Ser170Arg

c.508A>C · rs2493486826 · VCV3251849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4796	ambiguous
REVEL	0.566	indeterminate
SaProt	LLR -7.24	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 2,846 bp · p 0.42 · regional, not allelic
Overall
CADD	18.88	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,016 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,162 alleles · very rare exomes 3/1,461,892 · genomes 0/152,270 · 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.Ser170Arg
Coding: c.508A>C
MANE Select: NM_001083116
dbSNP: rs2493486826
Type: single nucleotide variant
Location: chr10:70600395 (GRCh38)
Gene constraint: LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.01
Residue 170: the macpf domain

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

Similar variants

PRF1 c.539+2T>A Pathogenic/Likely pathogenic ★★ same type
PRF1 p.Arg225Trp Pathogenic ★★ ⚠ same type
PRF1 p.Arg232Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
PRF1 p.Arg299Cys Pathogenic/Likely pathogenic ★★ same type
PRF1 p.Arg356Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
PRF1 p.Arg361Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
PRF1 p.Arg390Ter Pathogenic ★★ same type
PRF1 p.Arg410Pro Pathogenic/Likely pathogenic ★★ same type

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-ser170arg (accessed [today's date]).

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