PCGF2 p.Pro65=
c.195G>A · VCV3389257
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 -8.5 | GERP -3.9 |
| Overall | ||
| CADD | 5.465 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,060 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.00136%
22/1,613,378 alleles · ultra-rare
exomes 19/1,461,178 · genomes 3/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,030 |
| East Asian | 0.00223% | 44,864 |
| European (non-Finnish) | 0.00153% | 65,520 |
| South Asian | 0.0011% | 91,064 |
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
- PCGF2
- Protein
- p.Pro65=
- Coding
- c.195G>A
- MANE Select
- NM_007144
- Type
- single nucleotide variant
- Location
- chr17:38739600 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 75.30
- Residue 65
- a UniProt-annotated variant site (in tpfs)
Similar variants
- PCGF2 p.Pro65Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
- PCGF2 p.Pro65Ser Likely pathogenic ★★ same residue
- PCGF2 p.Pro65Arg Likely pathogenic ★ same residue
- PCGF2 p.Ala212Thr Uncertain significance ★★ ⚠ same type
- PCGF2 p.Arg45Cys Uncertain significance ★★ ⚠ same type
- PCGF2 p.Glu136Asp Uncertain significance ★★ ⚠ same type
- PCGF2 p.Glu198Lys Uncertain significance ★★ ⚠ same type
- PCGF2 p.Gly115Ser 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/pcgf2-p-pro65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown