Is PER2 p.Gly658= (c.1974C>T) pathogenic?

PER2 p.Gly658= (c.1974C>T) is classified Likely benign in PER2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-21). Ultra-rare (popmax 0.0164%, mid); Associated with PER2-related disorder.

What condition is associated with PER2 p.Gly658= (c.1974C>T)?

PER2 p.Gly658= (c.1974C>T) is associated with PER2-related disorder (ClinVar).

How common is PER2 p.Gly658= (c.1974C>T) in the general population?

PER2 p.Gly658= (c.1974C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PER2 p.Gly658=

c.1974C>T · rs772375894 · VCV3036487

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 4.2	GERP 0.54, phastCons 1
Overall
CADD	9.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00093% 15/1,613,472 alleles · ultra-rare exomes 14/1,461,234 · genomes 1/152,238 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0048%	20,825
African / African-American	0.00267%	37,473
European (non-Finnish)	0.000763%	131,100

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.Gly658=
Coding: c.1974C>T
MANE Select: NM_022817
dbSNP: rs772375894
Type: single nucleotide variant
Location: chr2:238257013 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.96 · 4 PDB
Residue 658: the 'csnk1e binding domain' region

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

Disease context

PER2-related disorder

Similar variants

PER2 p.Gly658Ser Likely benign ★ same residue
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

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-gly658 (accessed [today's date]).

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