PHF12 p.Pro653=
c.1959G>A · rs144144007 · VCV790330
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.38%, sas)
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 0.003 | GERP -1.5, phastCons 0.8 |
| Overall | ||
| CADD | 9.985 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.38%
South Asian · 2,170/91,082 alleles
Filtering AF
2.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.27%
Overall
0.318%
5,134/1,614,164 alleles · low-frequency
exomes 4,740/1,461,894 · genomes 394/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.38% | 42 |
| Ashkenazi Jewishnot grpmax-eligible | 0.871% | 115 |
| Middle Eastern | 0.627% | 160 |
| Finnishnot grpmax-eligible | 0.431% | 232 |
| Remaining individualsnot grpmax-eligible | 0.334% | 299 |
| European (non-Finnish) | 0.175% | 571 |
| Admixed American | 0.115% | 870 |
| African / African-American | 0.0587% | 1,705 |
| East Asian | 0.00891% | 11,220 |
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
- PHF12
- Protein
- p.Pro653=
- Coding
- c.1959G>A
- MANE Select
- NM_001033561
- dbSNP
- rs144144007
- Type
- single nucleotide variant
- Location
- chr17:28912612 (GRCh38)
- Gene constraint
- LOEUF 0.115 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.98 · 6 PDB
- Residue 653
- the 'interaction with sin3a' region; the 'disordered' region
Similar variants
- PHF12 p.Pro653Arg Uncertain significance ★ ⚠ same residue
- PHF12 p.Pro653Leu Uncertain significance ★ ⚠ same residue
- PHF12 p.Leu324Met Uncertain significance ★★ ⚠ same type
- PHF12 p.Ala152Ser Uncertain significance ★ ⚠ same type
- PHF12 p.Ala171Val Uncertain significance ★ ⚠ same type
- PHF12 p.Ala196Thr Uncertain significance ★ ⚠ same type
- PHF12 p.Ala36Thr Uncertain significance ★ ⚠ same type
- PHF12 p.Ala395Pro 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/phf12-p-pro653 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown