PHF8 p.Arg778=
c.2334G>A · rs146772565 · VCV735196
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0553%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.203 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -3.1 |
| Overall | ||
| CADD | 7.419 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0553%
European (non-Finnish) · 495/894,636 alleles
Filtering AF
0.0513%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0497%
Overall
0.0442%
535/1,209,381 alleles · ultra-rare
exomes 514/1,097,503 · genomes 21/111,878 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0553% | 1,807 |
| Remaining individualsnot grpmax-eligible | 0.042% | 2,379 |
| Admixed American | 0.0284% | 3,516 |
| African / African-American | 0.0122% | 8,170 |
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
- PHF8
- Protein
- p.Arg778=
- Coding
- c.2334G>A
- MANE Select
- NM_015107
- dbSNP
- rs146772565
- Type
- single nucleotide variant
- Location
- chrX:53985023 (GRCh38)
- Structure
- AlphaFold pLDDT 63.30 · 6 PDB
- Residue 778
- the 'disordered' region
Similar variants
- PHF8 p.Arg778Trp Uncertain significance ★ ⚠ same residue
- PHF8 p.Arg240Ter Likely pathogenic ★★ same type
- PHF8 p.Arg506Ter Pathogenic/Likely pathogenic ★★ same type
- PHF8 p.Arg753Ter Pathogenic/Likely pathogenic ★★ same type
- PHF8 p.Gln539Ter Pathogenic ★★ same type
- PHF8 p.Ser737Ter Pathogenic/Likely pathogenic ★★ same type
- PHF8 p.Ala770Pro Uncertain significance ★★ ⚠ same type
- PHF8 p.Ala888Ser 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/phf8-p-arg778 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown