Is PER2 p.Lys539= (c.1617A>G) pathogenic?

PER2 p.Lys539= (c.1617A>G) is classified Likely benign in PER2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-09). No allele count reported in gnomAD v4.1 (AN 1,439,366); Associated with PER2-related disorder.

What condition is associated with PER2 p.Lys539= (c.1617A>G)?

PER2 p.Lys539= (c.1617A>G) is associated with PER2-related disorder (ClinVar).

How common is PER2 p.Lys539= (c.1617A>G) in the general population?

PER2 p.Lys539= (c.1617A>G) is no allele count reported in gnomAD v4.1 (AN 1,439,366) (gnomAD).

PER2 p.Lys539=

c.1617A>G · rs2469820819 · VCV3049581

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,439,366)

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 -4.8	GERP -2.8
Overall
CADD	0.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,439,366). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PER2
Protein: p.Lys539=
Coding: c.1617A>G
MANE Select: NM_022817
dbSNP: rs2469820819
Type: single nucleotide variant
Location: chr2:238259979 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.96 · 4 PDB
Residue 539: the 'disordered' region; 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 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-lys539 (accessed [today's date]).

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