PER2 p.Leu993=
c.2979G>A · VCV4960753
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.275%, sas)
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 0.96 | GERP -1.6, phastCons 1 |
| Overall | ||
| CADD | 7.203 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.275%
South Asian · 250/91,066 alleles
Filtering AF
0.247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.236%
Overall
0.016%
258/1,613,820 alleles · rare
exomes 242/1,461,504 · genomes 16/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.275% | 364 |
| Middle Eastern | 0.0169% | 5,914 |
| East Asian | 0.00446% | 22,439 |
| African / African-American | 0.004% | 25,018 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
| European (non-Finnish) | 8.47e-05% | 1,179,956 |
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.Leu993=
- Coding
- c.2979G>A
- MANE Select
- NM_022817
- Type
- single nucleotide variant
- Location
- chr2:238253044 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 53.96 · 4 PDB
- Residue 993
- the 'interaction with pparg' region
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-leu993 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown