PHF8 p.Ala630=
c.1890G>A · VCV4951018
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00451%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.068 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -5 |
| Overall | ||
| CADD | 0.305 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00451%
Admixed American · 2/44,379 alleles
Filtering AF
0.000747%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000279%
Overall
0.000918%
11/1,198,763 alleles · very rare
exomes 9/1,087,120 · genomes 2/111,643 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00451% | 22,189 |
| South Asian | 0.00363% | 27,581 |
| European (non-Finnish) | 0.000788% | 126,899 |
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.Ala630=
- Coding
- c.1890G>A
- MANE Select
- NM_015107
- Type
- single nucleotide variant
- Location
- chrX:53987785 (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-ala630 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown