PHF8 p.Arg380=
c.1140C>T · VCV3772692
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0149%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.205 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.60 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 3.6 | GERP 0.69, phastCons 1 |
| Overall | ||
| CADD | 15.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0149%
East Asian · 5/33,540 alleles
Filtering AF
0.00584%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00375%
Overall
0.00104%
12/1,154,625 alleles · ultra-rare
exomes 10/1,043,861 · genomes 2/110,764 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0149% | 6,708 |
| European (non-Finnish) | 0.000828% | 120,780 |
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.Arg380=
- Coding
- c.1140C>T
- MANE Select
- NM_015107
- Type
- single nucleotide variant
- Location
- chrX:54002156 (GRCh38)
- Structure
- AlphaFold pLDDT 63.30 · 6 PDB
- Residue 380
- the jmjc domain; an α-helix
Similar variants
- 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
- PHF8 p.Arg240Gln 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-arg380 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown