PHF8 p.Asp554=
c.1662T>C · rs782325007 · VCV730179
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0406%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.081 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.18 | GERP -4.9 |
| Overall | ||
| CADD | 2.852 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0406%
African / African-American · 23/56,689 alleles
Filtering AF
0.0277%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0235%
Overall
0.00208%
25/1,201,929 alleles · ultra-rare
exomes 17/1,091,269 · genomes 8/110,660 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0406% | 2,465 |
| Admixed American | 0.0022% | 45,470 |
| European (non-Finnish) | 0.000112% | 889,166 |
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.Asp554=
- Coding
- c.1662T>C
- MANE Select
- NM_015107
- dbSNP
- rs782325007
- Type
- single nucleotide variant
- Location
- chrX:53992804 (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-asp554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown