PER2 p.Ala655=
c.1965A>G · rs2304669 · VCV1246724
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 19.1%, amr) — 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 -14 | GERP -3.9 |
| Overall | ||
| CADD | 0.437 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
19.1%
Admixed American · 11,478/60,008 alleles
Filtering AF
18.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 18.7%
Overall
13.2%
213,336/1,613,266 alleles · common
exomes 195,981/1,460,996 · genomes 17,355/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 19.1% | 5 |
| Amishnot grpmax-eligible | 18.4% | 5 |
| Finnishnot grpmax-eligible | 16.5% | 6 |
| European (non-Finnish) | 14.2% | 7 |
| Remaining individualsnot grpmax-eligible | 12.2% | 8 |
| East Asian | 12% | 8 |
| Ashkenazi Jewishnot grpmax-eligible | 9.5% | 11 |
| Middle Eastern | 7.43% | 13 |
| South Asian | 5.37% | 19 |
| African / African-American | 3.4% | 29 |
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.Ala655=
- Coding
- c.1965A>G
- MANE Select
- NM_022817
- dbSNP
- rs2304669
- Type
- single nucleotide variant
- Location
- chr2:238257022 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 53.96 · 4 PDB
- Residue 655
- the 'csnk1e binding domain' region
Similar variants
- PER2 p.Arg401His Uncertain significance ★★ ⚠ same type
- PER2 p.Glu184Ala Uncertain significance ★★ ⚠ 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
- PER2 p.Phe393= Benign ★★ same type
- PER2 p.Pro822= 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-ala655 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown