PHF2 p.Pro273=
c.819G>A · rs758231547 · VCV3041221
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0227%, afr)
Conditions
1
PHF2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.9 | GERP -3.5 |
| Overall | ||
| CADD | 4.303 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0227%
African / African-American · 17/74,910 alleles
Filtering AF
0.0144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0119%
Overall
0.00397%
64/1,613,622 alleles · ultra-rare
exomes 51/1,461,466 · genomes 13/152,156 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0227% | 4,406 |
| East Asian | 0.0201% | 4,986 |
| Admixed American | 0.0167% | 6,000 |
| South Asian | 0.00769% | 13,011 |
| European (non-Finnish) | 0.0017% | 58,996 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,464 |
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
- PHF2
- Protein
- p.Pro273=
- Coding
- c.819G>A
- MANE Select
- NM_005392
- dbSNP
- rs758231547
- Type
- single nucleotide variant
- Location
- chr9:93654442 (GRCh38)
- Gene constraint
- LOEUF 0.329 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.14 · 9 PDB
- Residue 273
- the jmjc domain
Disease context
PHF2-related disorder
Similar variants
- PHF2 p.Gly527Ser Uncertain significance ★ ⚠ same condition
- PHF2 p.Ser1020Thr Uncertain significance ★ ⚠ same condition
- PHF2 p.Asp133= Likely benign same condition
- PHF2 p.Gly629= Likely benign same condition
- PHF2 p.His865= Likely benign same condition
- PHF2 p.Leu548= Benign same condition
- PHF2 p.Lys890= Likely benign same condition
- PHF2 p.Pro480Leu Likely benign same condition
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/phf2-p-pro273 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown