Is PRF1 p.Pro382Ser (c.1144C>T) pathogenic?

PRF1 p.Pro382Ser (c.1144C>T) is classified Uncertain significance in PRF1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0876); Ultra-rare (popmax 0.027%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRF1 p.Pro382Ser (c.1144C>T)?

PRF1 p.Pro382Ser (c.1144C>T) is associated with Inborn genetic diseases, familial hemophagocytic lymphohistiocytosis 2 (ClinVar).

How common is PRF1 p.Pro382Ser (c.1144C>T) in the general population?

PRF1 p.Pro382Ser (c.1144C>T) is ultra-rare (popmax 0.027%, nfe) (gnomAD).

What do computational predictors say about PRF1 p.Pro382Ser (c.1144C>T)?

AlphaMissense predicts likely benign (score 0.0876) — an in-silico prediction, not a clinical call.

PRF1 p.Pro382Ser

c.1144C>T · rs377367451 · VCV639746

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0876 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.027%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0876	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -8.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 2,846 bp · p 0.42 · regional, not allelic
Overall
CADD	18.52	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.027% European (non-Finnish) · 318/1,179,766 alleles

Filtering AF 0.0245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0235%

Overall 0.0205% 331/1,612,454 alleles · ultra-rare exomes 316/1,460,306 · genomes 15/152,148 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.027%	3,710
Remaining individualsnot grpmax-eligible	0.0128%	7,802
African / African-American	0.00668%	14,981

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.Pro382Ser
Coding: c.1144C>T
MANE Select: NM_001083116
dbSNP: rs377367451
Type: single nucleotide variant
Location: chr10:70598577 (GRCh38)
Gene constraint: LOEUF 1.438 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.01
Residue 382: the egf-like 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

Also linked: familial hemophagocytic lymphohistiocytosis 2

Similar variants

PRF1 p.Pro382= Likely benign ★ 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-pro382ser (accessed [today's date]).

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