PHF6 p.Gly331Arg
c.991G>A · VCV4885480
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9614 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9614 | likely pathogenic |
|---|---|---|
| REVEL | 0.452 | indeterminate |
| SaProt | LLR -4.52 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate. | ||
| Splicing | ||
| SpliceAI | Δ0.33 | acceptor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.8, phastCons 1 |
| Regional constraint | o/e 0.17 | constrained · MANE · 11 kb · p 1e-15 · 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.
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.Gly331Arg
- Coding
- c.991G>A
- MANE Select
- NM_001015877
- Type
- single nucleotide variant
- Location
- chrX:134425223 (GRCh38)
- Structure
- AlphaFold pLDDT 73.45 · 2 PDB
- Residue 331
- the 'disordered' region
Similar variants
- PHF6 p.Arg116Ter Pathogenic ★★ same type
- PHF6 p.Arg225Ter Pathogenic ★★ same type
- PHF6 p.Arg274Ter Pathogenic ★★ same type
- PHF6 p.Arg342Ter Pathogenic ★★ same type
- PHF6 p.Cys45Tyr Pathogenic ★★ same type
- PHF6 p.Met1Thr Pathogenic ★★ same type
- PHF6 p.Arg163His Uncertain significance ★★ ⚠ same type
- PHF6 p.Arg166Lys 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/phf6-p-gly331arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown