PYCR1 p.Pro76=
c.228C>T · rs377342114 · VCV514289
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, 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 1.7 | GERP 0.56, phastCons 1 |
| Overall | ||
| CADD | 10.96 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
African / African-American · 11/74,930 alleles
Filtering AF
0.00815%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00633%
Overall
0.000806%
13/1,613,566 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0147% | 6,812 |
| European (non-Finnish) | 0.000169% | 589,991 |
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
- PYCR1
- Protein
- p.Pro76=
- Coding
- c.228C>T
- MANE Select
- NM_006907
- dbSNP
- rs377342114
- Type
- single nucleotide variant
- Location
- chr17:81935427 (GRCh38)
- Gene constraint
- LOEUF 1.268 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.98 · 47 PDB
- Residue 76
- an α-helix
Similar variants
- PYCR1 c.138+1G>A Pathogenic/Likely pathogenic ★★ same type
- PYCR1 c.540+1G>A Pathogenic ★★ same type
- PYCR1 c.633+1G>C Pathogenic/Likely pathogenic ★★ same type
- PYCR1 c.67+2T>A Pathogenic ★★ same type
- PYCR1 p.Ala179Thr Pathogenic/Likely pathogenic ★★ same type
- PYCR1 p.Arg119Cys Pathogenic/Likely pathogenic ★★ same type
- PYCR1 p.Arg119Gly Pathogenic/Likely pathogenic ★★ same type
- PYCR1 p.Arg119His Pathogenic/Likely pathogenic ★★ 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/pycr1-p-pro76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown