Is PER2 p.Thr1004= (c.3012T>C) pathogenic?

PER2 p.Thr1004= (c.3012T>C) is classified Likely benign in PER2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-30). Rare (popmax 0.271%, afr); Associated with PER2-related disorder.

What condition is associated with PER2 p.Thr1004= (c.3012T>C)?

PER2 p.Thr1004= (c.3012T>C) is associated with PER2-related disorder (ClinVar).

How common is PER2 p.Thr1004= (c.3012T>C) in the general population?

PER2 p.Thr1004= (c.3012T>C) is rare (popmax 0.271%, afr) (gnomAD).

PER2 p.Thr1004=

c.3012T>C · rs142267174 · VCV3049516

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.271%, afr)

Conditions

PER2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -3
Overall
CADD	0.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.271% African / African-American · 203/75,030 alleles

Filtering AF 0.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.228%

Overall 0.0138% 223/1,613,880 alleles · rare exomes 100/1,461,626 · genomes 123/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.271%	370
Remaining individualsnot grpmax-eligible	0.016%	6,250
Admixed American	0.015%	6,668
European (non-Finnish)	8.47e-05%	1,179,981

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: PER2
Protein: p.Thr1004=
Coding: c.3012T>C
MANE Select: NM_022817
dbSNP: rs142267174
Type: single nucleotide variant
Location: chr2:238253011 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.96 · 4 PDB
Residue 1004: the 'interaction with pparg' region

Full PER2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PER2-related disorder

Similar variants

PER2 c.3275-1G>A Uncertain significance ★ same condition
PER2 c.1153+10C>G Likely benign same condition
PER2 c.1542+4C>T Likely benign same condition
PER2 c.1775+4T>C Likely benign same condition
PER2 c.448+8G>T Likely benign same condition
PER2 p.Ala664= Benign same condition
PER2 p.Ala664Val Benign same condition
PER2 p.Ala695= Likely benign 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/per2-p-thr1004 (accessed [today's date]).

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