PYCR1 p.Pro178=
c.534C>T · rs757228455 · VCV1927927
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
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 -3.5 | GERP -3.9 |
| Overall | ||
| CADD | 4.932 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,010 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00174%
28/1,609,280 alleles · very rare
exomes 26/1,457,072 · genomes 2/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,168 |
| Remaining individualsnot grpmax-eligible | 0.00482% | 20,763 |
| East Asian | 0.00446% | 22,442 |
| African / African-American | 0.00401% | 24,951 |
| European (non-Finnish) | 0.00119% | 84,282 |
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.Pro178=
- Coding
- c.534C>T
- MANE Select
- NM_006907
- dbSNP
- rs757228455
- Type
- single nucleotide variant
- Location
- chr17:81934932 (GRCh38)
- Gene constraint
- LOEUF 1.268 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.98 · 47 PDB
- Residue 178
- 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-pro178 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown