PHF21A p.Pro69=
c.207G>A · rs781277394 · VCV1963388
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -0.39 | GERP -3.8, phastCons 0.17 |
| Overall | ||
| CADD | 11.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.000738%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000558%
9/1,614,000 alleles · ultra-rare
exomes 7/1,461,876 · genomes 2/152,124 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| East Asian | 0.00445% | 22,448 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
| Finnishnot grpmax-eligible | 0.00156% | 64,032 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000254% | 393,343 |
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
- PHF21A
- Protein
- p.Pro69=
- Coding
- c.207G>A
- MANE Select
- NM_001352027
- dbSNP
- rs781277394
- Type
- single nucleotide variant
- Location
- chr11:45979913 (GRCh38)
- Gene constraint
- LOEUF 0.149 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.12 · 2 PDB
Similar variants
- PHF21A p.Pro69Leu Uncertain significance ★ ⚠ same residue
- PHF21A p.Pro69Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- PHF21A p.Pro69Thr Uncertain significance ★ ⚠ same residue
- PHF21A p.Arg391Ter Pathogenic/Likely pathogenic ★★ same type
- PHF21A p.Arg581Ter Pathogenic/Likely pathogenic ★★ same type
- PHF21A p.Gln75Ter Pathogenic ★★ same type
- PHF21A p.Gln88Ter Pathogenic/Likely pathogenic ★★ same type
- PHF21A p.Lys392Ter Pathogenic ★★ 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/phf21a-p-pro69 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown