PYGB p.Val415=
c.1245G>A · rs35073849 · VCV769084
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.81%, afr)
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 2.1 | GERP -0.81, phastCons 1 |
| Overall | ||
| CADD | 2.622 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.81%
African / African-American · 2,109/75,036 alleles
Filtering AF
2.71%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.67%
Overall
0.149%
2,408/1,613,872 alleles · low-frequency
exomes 1,185/1,461,572 · genomes 1,223/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.81% | 36 |
| Remaining individualsnot grpmax-eligible | 0.234% | 428 |
| Middle Eastern | 0.182% | 550 |
| Admixed American | 0.145% | 690 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0338% | 2,959 |
| European (non-Finnish) | 0.00356% | 28,092 |
| South Asian | 0.00329% | 30,353 |
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
- PYGB
- Protein
- p.Val415=
- Coding
- c.1245G>A
- MANE Select
- NM_002862
- dbSNP
- rs35073849
- Type
- single nucleotide variant
- Location
- chr20:25280954 (GRCh38)
- Gene constraint
- LOEUF 1.021 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.71 · 2 PDB
- Residue 415
- an α-helix
Similar variants
- PYGB p.Val415Met Uncertain significance ★ ⚠ same residue
- PYGB p.Ala57Gly Likely benign ★★ same type
- PYGB p.Ala180Gly Uncertain significance ★ ⚠ same type
- PYGB p.Ala247Ser Uncertain significance ★ ⚠ same type
- PYGB p.Ala249Val Uncertain significance ★ ⚠ same type
- PYGB p.Ala302Thr Uncertain significance ★ ⚠ same type
- PYGB p.Ala406Ser Uncertain significance ★ ⚠ same type
- PYGB p.Ala611Val Uncertain significance ★ ⚠ 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/pygb-p-val415 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown