PHF8 p.Arg753Ter
c.2257C>T · rs2519516307 · VCV1878824
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
syndromic X-linked intellectual disability Siderius type
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 18 of 22 |
| REVEL | 0.009 | strongly benign-leaning |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.1 | GERP 0.45, phastCons 1 |
| Overall | ||
| CADD | 35.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PHF8
- Protein
- p.Arg753Ter
- Coding
- c.2257C>T
- MANE Select
- NM_015107
- dbSNP
- rs2519516307
- Type
- single nucleotide variant
- Location
- chrX:53985100 (GRCh38)
- Structure
- AlphaFold pLDDT 63.30 · 6 PDB
Similar variants
- PHF8 p.Arg753Gln Uncertain significance ★★ ⚠ same residue
- PHF8 p.Arg240Ter Likely pathogenic ★★ same condition
- PHF8 p.Arg506Ter Pathogenic/Likely pathogenic ★★ same condition
- PHF8 p.Arg66His Uncertain significance ★★ ⚠ same condition
- PHF8 p.Arg773Pro Uncertain significance ★★ ⚠ same condition
- PHF8 p.Leu949Phe Uncertain significance ★★ ⚠ same condition
- PHF8 p.Tyr706Cys Uncertain significance ★★ ⚠ same condition
- PHF8 c.2650-35C>G Benign ★★ 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-arg753ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown