PER3 p.Ala504Val
c.1511C>T · rs777226760 · VCV793011
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.083 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.23 | donor loss · deltas |
| Pangolin | Δ0.22 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.03 | GERP 0.68 |
| Regional constraint | o/e 1.09 | unconstrained · MANE · 45 kb · p 0.002 · regional, not allelic |
| Overall | ||
| CADD | 7.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,068 alleles
Filtering AF
0.00367%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00329%
Overall
0.00385%
62/1,608,946 alleles · ultra-rare
exomes 56/1,456,964 · genomes 6/151,982 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,068 |
| South Asian | 0.00555% | 18,014 |
| European (non-Finnish) | 0.00467% | 21,425 |
| African / African-American | 0.00134% | 74,654 |
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
- PER3
- Protein
- p.Ala504Val
- Coding
- c.1511C>T
- MANE Select
- NM_001377275
- dbSNP
- rs777226760
- Type
- single nucleotide variant
- Location
- chr1:7810577 (GRCh38)
- Gene constraint
- LOEUF 1.009 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.62
Similar variants
- PER3 p.Arg157His Uncertain significance ★★ ⚠ same type
- PER3 p.Asn572Thr Uncertain significance ★★ ⚠ same type
- PER3 p.Ala980= Benign ★★ same type
- PER3 p.Cys1185Ser Benign ★★ same type
- PER3 p.Ile614= Benign ★★ same type
- PER3 p.Leu937= Likely benign ★★ same type
- PER3 p.Thr527Ala Likely benign ★★ same type
- PER3 p.Thr983= Benign/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/per3-p-ala504val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown