PHF2 p.Leu645=
c.1935C>T · rs138464551 · VCV733486
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.208%, nfe)
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 -0.44 | GERP -2.8, phastCons 0.004 |
| Overall | ||
| CADD | 1.687 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.208%
European (non-Finnish) · 2,434/1,168,006 alleles
Filtering AF
0.201%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.199%
Overall
0.171%
2,733/1,598,720 alleles · rare
exomes 2,512/1,446,590 · genomes 221/152,130 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.208% | 480 |
| Finnishnot grpmax-eligible | 0.165% | 607 |
| Remaining individualsnot grpmax-eligible | 0.147% | 680 |
| Admixed American | 0.115% | 873 |
| Middle Eastern | 0.0331% | 3,020 |
| African / African-American | 0.0322% | 3,103 |
| South Asian | 0.00999% | 10,009 |
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.Leu645=
- Coding
- c.1935C>T
- MANE Select
- NM_005392
- dbSNP
- rs138464551
- Type
- single nucleotide variant
- Location
- chr9:93663633 (GRCh38)
- Gene constraint
- LOEUF 0.329 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.14 · 9 PDB
Similar variants
- PHF2 c.299+7T>A Benign ★★ same type
- PHF2 c.789+10G>A Benign/Likely benign ★★ same type
- PHF2 p.Asp103= Benign ★★ same type
- PHF2 p.Pro786= Benign ★★ same type
- PHF2 p.Pro988= Benign ★★ same type
- PHF2 p.Ser725= Benign ★★ same type
- PHF2 p.Ser738= Benign ★★ same type
- PHF2 p.Thr124= Benign ★★ 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/phf2-p-leu645 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown