PYCR2 p.Ala96=
c.288G>A · rs148023221 · VCV734289
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.973%, mid)
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 -13 | GERP -3.6 |
| Overall | ||
| CADD | 6.357 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.973%
Middle Eastern · 59/6,062 alleles
Filtering AF
0.775%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.703%
Overall
0.0261%
422/1,614,120 alleles · rare
exomes 391/1,461,792 · genomes 31/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.973% | 103 |
| Ashkenazi Jewishnot grpmax-eligible | 0.287% | 348 |
| South Asian | 0.116% | 859 |
| Remaining individualsnot grpmax-eligible | 0.0576% | 1,736 |
| Admixed American | 0.0267% | 3,752 |
| European (non-Finnish) | 0.01% | 10,000 |
| African / African-American | 0.00266% | 37,527 |
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
- PYCR2
- Protein
- p.Ala96=
- Coding
- c.288G>A
- MANE Select
- NM_013328
- dbSNP
- rs148023221
- Type
- single nucleotide variant
- Location
- chr1:225922234 (GRCh38)
- Gene constraint
- LOEUF 1.029 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.60 · 2 PDB
- Residue 96
- a binding site
Similar variants
- PYCR2 p.Arg119Cys Pathogenic/Likely pathogenic ★★ same type
- PYCR2 p.Arg119His Likely pathogenic ★★ same type
- PYCR2 p.Arg266Ter Pathogenic ★★ same type
- PYCR2 p.Gln226Ter Pathogenic/Likely pathogenic ★★ same type
- PYCR2 p.Ala187Thr Uncertain significance ★★ ⚠ same type
- PYCR2 p.Arg17Pro Uncertain significance ★★ ⚠ same type
- PYCR2 p.Arg200Cys Uncertain significance ★★ ⚠ same type
- PYCR2 p.Ile82Thr 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/pycr2-p-ala96 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown