PYCR2 p.Ser220=
c.660G>A · rs780599845 · VCV2639968
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0143%, nfe)
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 -20 | GERP -3.6 |
| Overall | ||
| CADD | 0.216 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0143%
European (non-Finnish) · 161/1,125,364 alleles
Filtering AF
0.0125%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0118%
Overall
0.0108%
168/1,553,408 alleles · ultra-rare
exomes 165/1,401,268 · genomes 3/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0143% | 6,990 |
| African / African-American | 0.00408% | 24,495 |
| South Asian | 0.00223% | 44,845 |
| Admixed American | 0.00167% | 59,822 |
| Remaining individualsnot grpmax-eligible | 0.00165% | 60,520 |
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.Ser220=
- Coding
- c.660G>A
- MANE Select
- NM_013328
- dbSNP
- rs780599845
- Type
- single nucleotide variant
- Location
- chr1:225921345 (GRCh38)
- Gene constraint
- LOEUF 1.029 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.60 · 2 PDB
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-ser220 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown