PCNA p.Phe215=
c.645T>C · rs746973454 · VCV749190
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00331%, nfe)
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 1.2 | GERP -3.7, phastCons 1 |
| Overall | ||
| CADD | 8.315 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00331%
European (non-Finnish) · 39/1,179,816 alleles
Filtering AF
0.00247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00217%
Overall
0.00248%
40/1,613,828 alleles · very rare
exomes 39/1,461,594 · genomes 1/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00331% | 30,252 |
| Admixed American | 0.00167% | 60,008 |
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
- PCNA
- Protein
- p.Phe215=
- Coding
- c.645T>C
- MANE Select
- NM_182649
- dbSNP
- rs746973454
- Type
- single nucleotide variant
- Location
- chr20:5115510 (GRCh38)
- Gene constraint
- LOEUF 0.42 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 94.38 · 103 PDB
- Residue 215
- an α-helix
Similar variants
- PCNA p.Cys148Ser Likely pathogenic ★★ same type
- PCNA p.Ser228Ile Uncertain significance ★★ ⚠ same type
- PCNA p.Ala242= Benign/Likely benign ★★ same type
- PCNA p.Pro234= Benign ★★ same type
- PCNA p.Arg53Gln Uncertain significance ★ ⚠ same type
- PCNA p.Asn24Ser Uncertain significance ★ ⚠ same type
- PCNA p.Gly56Ser Uncertain significance ★ ⚠ same type
- PCNA p.Leu182Phe 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/pcna-p-phe215 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown