PHF8 p.Arg438His
c.1313G>A · rs781871345 · VCV1693395
Computational evidence
| Protein change | ||
| AlphaMissense | 0.556 | ambiguous |
|---|---|---|
| REVEL | 0.309 | indeterminate |
| SaProt | LLR -10.58 | damaging |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.8, phastCons 1 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 12 kb · p 0.36 · regional, not allelic |
| Overall | ||
| CADD | 25.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R474H vs ClinVar R438H) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.00214% | 46,783 |
| European (non-Finnish)grpmax | 0.000115% | 871,186 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg438His
- Coding
- c.1313G>A
- MANE Select
- NM_015107
- dbSNP
- rs781871345
- Type
- single nucleotide variant
- Location
- chrX:53995703 (GRCh38)
- Structure
- AlphaFold pLDDT 63.30 · 6 PDB
- Residue 438
- an α-helix
Similar variants
- PHF8 p.Arg438Cys Likely pathogenic ★ same residue
- PHF8 p.Arg506Ter Pathogenic/Likely pathogenic ★★ same condition
- PHF8 p.Ala770Pro Uncertain significance ★★ ⚠ same condition
- PHF8 p.Arg240Gln Uncertain significance ★★ ⚠ same condition
- PHF8 p.Arg588Gln Uncertain significance ★★ ⚠ same condition
- PHF8 p.Arg773Pro Uncertain significance ★★ ⚠ same condition
- PHF8 p.Arg968Cys Uncertain significance ★★ ⚠ same condition
- PHF8 p.Arg982Trp Uncertain significance ★★ ⚠ same condition
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-arg438his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown