Is PRF1 p.Ser271Cys (c.811A>T) pathogenic?

PRF1 p.Ser271Cys (c.811A>T) is classified Uncertain significance in PRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: likely benign (0.2981); Very rare (popmax 0.000508%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRF1 p.Ser271Cys (c.811A>T)?

PRF1 p.Ser271Cys (c.811A>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRF1 p.Ser271Cys (c.811A>T) in the general population?

PRF1 p.Ser271Cys (c.811A>T) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about PRF1 p.Ser271Cys (c.811A>T)?

AlphaMissense predicts likely benign (score 0.2981) — an in-silico prediction, not a clinical call.

PRF1 p.Ser271Cys

c.811A>T · VCV3309889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2981	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -11.54	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.055	GERP -0.003
Regional constraint	o/e 0.97	unconstrained · MANE · 2,846 bp · p 0.42 · regional, not allelic
Overall
CADD	16.63	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 0.000508% European (non-Finnish) · 6/1,180,038 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00041% 6/1,461,884 alleles · very rare

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.Ser271Cys
Coding: c.811A>T
MANE Select: NM_001083116
Type: single nucleotide variant
Location: chr10:70598910 (GRCh38)
Gene constraint: LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.01
Residue 271: a disulfide bond; the macpf domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRF1 p.Gly149Ser Pathogenic ★★ ⚠ same condition
PRF1 p.Arg104Cys Uncertain significance ★★ ⚠ same condition
PRF1 p.Arg123Cys Uncertain significance ★★ ⚠ same condition
PRF1 p.Arg214Gly Uncertain significance ★★ ⚠ same condition
PRF1 p.Arg464Trp Uncertain significance ★★ ⚠ same condition
PRF1 p.Arg550Trp Uncertain significance ★★ ⚠ same condition
PRF1 p.Arg55His Uncertain significance ★★ ⚠ same condition
PRF1 p.Arg96Trp Uncertain significance ★★ ⚠ 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-ser271cys (accessed [today's date]).

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