PER2 p.Lys226=
c.678G>A · rs116439936 · VCV791898
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.24%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.53 | GERP -5.5, phastCons 1 |
| Overall | ||
| CADD | 7.978 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.24%
African / African-American · 933/75,074 alleles
Filtering AF
1.18%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.15%
Overall
0.0642%
1,037/1,614,178 alleles · low-frequency
exomes 514/1,461,782 · genomes 523/152,396 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.24% | 80 |
| Remaining individualsnot grpmax-eligible | 0.0688% | 1,454 |
| Admixed American | 0.0583% | 1,715 |
| Middle Eastern | 0.033% | 3,031 |
| South Asian | 0.00878% | 11,386 |
| European (non-Finnish) | 0.00136% | 73,747 |
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.Lys226=
- Coding
- c.678G>A
- MANE Select
- NM_022817
- dbSNP
- rs116439936
- Type
- single nucleotide variant
- Location
- chr2:238271406 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 53.96 · 4 PDB
- Residue 226
- the pas 1 domain
Similar variants
- 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
- PER2 p.Phe393= 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-lys226 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown