PHF6 p.Arg274Ter
c.820C>T · rs1556019107 · VCV521446
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Inborn genetic diseases
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 8 of 11 |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 37.0 | 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
- PHF6
- Protein
- p.Arg274Ter
- Coding
- c.820C>T
- MANE Select
- NM_001015877
- dbSNP
- rs1556019107
- Type
- single nucleotide variant
- Location
- chrX:134415106 (GRCh38)
- Structure
- AlphaFold pLDDT 73.45 · 2 PDB
- Residue 274
- an α-helix; the 'extended phd2 domain (ephd2)' region
Similar variants
- PHF6 p.Arg274Gln Uncertain significance ★ ⚠ same residue
- PHF6 p.Arg116Ter Pathogenic ★★ same condition
- PHF6 p.Arg225Ter Pathogenic ★★ same condition
- PHF6 p.Arg342Ter Pathogenic ★★ same condition
- PHF6 p.Cys45Tyr Pathogenic ★★ same condition
- PHF6 p.Met1Thr Pathogenic ★★ same condition
- PHF6 p.Arg163His Uncertain significance ★★ ⚠ same condition
- PHF6 p.Arg166Lys 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/phf6-p-arg274ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown