PHF6 p.Lys44=
c.132G>A · rs759708359 · VCV728761
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0356%, eas)
Conditions
1
Borjeson-Forssman-Lehmann syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP 0.21, phastCons 1 |
| Overall | ||
| CADD | 6.802 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0356%
East Asian · 12/33,699 alleles
Filtering AF
0.0205%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0161%
Overall
0.00182%
22/1,206,287 alleles · ultra-rare
exomes 20/1,096,469 · genomes 2/109,818 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0356% | 2,808 |
| Remaining individualsnot grpmax-eligible | 0.0168% | 5,937 |
| Admixed American | 0.0022% | 45,406 |
| South Asian | 0.00176% | 56,697 |
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
- PHF6
- Protein
- p.Lys44=
- Coding
- c.132G>A
- MANE Select
- NM_001015877
- dbSNP
- rs759708359
- Type
- single nucleotide variant
- Location
- chrX:134377749 (GRCh38)
- Structure
- AlphaFold pLDDT 73.45 · 2 PDB
- Residue 44
- the 'extended phd1 domain (ephd1)' region
Similar variants
- PHF6 p.Arg116Ter Pathogenic ★★ same condition
- PHF6 p.Arg225Ter Pathogenic ★★ same condition
- PHF6 p.Arg274Ter 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-lys44 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown