PYCR2 p.Val193=
c.579G>A · rs1671841865 · VCV1922587
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | acceptor loss · deltas |
|---|---|---|
| Pangolin | Δ0.27 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 0.8, phastCons 1 |
| Overall | ||
| CADD | 6.937 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,002 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000186%
3/1,614,114 alleles · very rare
exomes 1/1,461,888 · genomes 2/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,001 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
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.Val193=
- Coding
- c.579G>A
- MANE Select
- NM_013328
- dbSNP
- rs1671841865
- Type
- single nucleotide variant
- Location
- chr1:225921606 (GRCh38)
- Gene constraint
- LOEUF 1.029 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.60 · 2 PDB
- Residue 193
- an α-helix
Similar variants
- PYCR2 p.Val193Met Likely pathogenic ★ same residue
- 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
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-val193 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown