PHF8 p.Ser139=
c.417G>A · VCV4951028
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0229%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.145 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.82 | phastCons 0.005 |
| Overall | ||
| CADD | 2.596 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0229%
Middle Eastern · 1/4,358 alleles
Filtering AF
0.00235%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00141%
Overall
0.000912%
11/1,205,876 alleles · ultra-rare
exomes 7/1,094,262 · genomes 4/111,614 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0229% | 4,358 |
| South Asian | 0.00706% | 14,173 |
| African / African-American | 0.00702% | 14,243 |
| Remaining individualsnot grpmax-eligible | 0.00211% | 47,464 |
| European (non-Finnish) | 0.000112% | 891,695 |
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.Ser139=
- Coding
- c.417G>A
- MANE Select
- NM_015107
- Type
- single nucleotide variant
- Location
- chrX:54017698 (GRCh38)
- Structure
- AlphaFold pLDDT 63.30 · 6 PDB
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-ser139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown