PER2 p.Ser665=
c.1995G>A · rs2304671 · VCV1278506
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 11.4%, sas) — too common for a highly-penetrant pathogenic allele
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 -0.19 | GERP -1.4, phastCons 0.061 |
| Overall | ||
| CADD | 7.713 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.4%
South Asian · 10,357/91,056 alleles
Filtering AF
11.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11.1%
Overall
5.64%
90,987/1,613,494 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 11.4% | 9 |
| East Asian | 11.2% | 9 |
| Finnishnot grpmax-eligible | 8.82% | 11 |
| African / African-American | 6.34% | 16 |
| Middle Eastern | 6.14% | 16 |
| Remaining individualsnot grpmax-eligible | 5.73% | 17 |
| European (non-Finnish) | 4.99% | 20 |
| Admixed American | 2.71% | 37 |
| Ashkenazi Jewishnot grpmax-eligible | 2.67% | 38 |
| Amishnot grpmax-eligible | 1.54% | 65 |
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.Ser665=
- Coding
- c.1995G>A
- MANE Select
- NM_022817
- dbSNP
- rs2304671
- Type
- single nucleotide variant
- Location
- chr2:238256992 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 53.96 · 4 PDB
- Residue 665
- the 'csnk1e binding domain' region
Similar variants
- PER2 p.Ser665Pro Uncertain significance ★ ⚠ same residue
- PER2 p.Arg401His Uncertain significance ★★ ⚠ same type
- PER2 p.Glu184Ala Uncertain significance ★★ ⚠ same type
- PER2 p.Ala655= Benign ★★ same type
- PER2 p.Arg401Cys Benign ★★ same type
- PER2 p.Arg820= Likely benign ★★ same type
- PER2 p.Cys1084Arg Likely benign ★★ same type
- PER2 p.His476Asn Likely 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/per2-p-ser665 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown