Is PER3 p.Arg50fs (c.150_151del) pathogenic?

PER3 p.Arg50fs (c.150151del) is classified Uncertain significance in PER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-06). Very rare (popmax 0.0033%, sas); Associated with advanced sleep phase syndrome 3.

What condition is associated with PER3 p.Arg50fs (c.150_151del)?

PER3 p.Arg50fs (c.150_151del) is associated with advanced sleep phase syndrome 3 (ClinVar).

How common is PER3 p.Arg50fs (c.150_151del) in the general population?

PER3 p.Arg50fs (c.150_151del) is very rare (popmax 0.0033%, sas) (gnomAD).

How is Familial advanced sleep-phase syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PER3 p.Arg50fs

c.150_151del · VCV3891938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Conditions

advanced sleep phase syndrome 3

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 3 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.087	GERP -2.8, phastCons 0.004

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/91,026 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000372% 6/1,612,606 alleles · very rare exomes 6/1,460,392 · genomes 0/152,214 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,342
European (non-Finnish)	0.000255%	392,907

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: PER3
Protein: p.Arg50fs
Coding: c.150_151del
MANE Select: NM_001377275
Type: Microsatellite
Location: chr1:7785460 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.62
Residue 50: the 'disordered' region

Full PER3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

advanced sleep phase syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial advanced sleep-phase syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

Similar variants

PER3 p.Asn572Thr Uncertain significance ★★ ⚠ same condition
PER3 c.3550-1G>A Uncertain significance ★ same condition
PER3 p.His417Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
PER3 p.Met57Ile Uncertain significance ★ ⚠ same condition
PER3 p.Pro415Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
PER3 c.1512_1522+10del Likely benign ★ same type
PER3 p.998ALSTGSPPMKNPSHPTAS[1] Benign ★ 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/per3-p-arg50fs (accessed [today's date]).

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