PHF6 p.Ala41=
c.123G>A · rs573685409 · VCV1757918
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0229%, mid)
Conditions
1
Inborn genetic diseases
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 4 | GERP -0.29, phastCons 1 |
| Overall | ||
| CADD | 9.057 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0229%
Middle Eastern · 1/4,367 alleles
Filtering AF
0.00342%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00218%
Overall
0.000995%
12/1,206,007 alleles · ultra-rare
exomes 8/1,096,743 · genomes 4/109,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0229% | 4,367 |
| African / African-American | 0.00887% | 11,278 |
| Finnishnot grpmax-eligible | 0.00218% | 45,821 |
| European (non-Finnish) | 0.00056% | 178,712 |
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.Ala41=
- Coding
- c.123G>A
- MANE Select
- NM_001015877
- dbSNP
- rs573685409
- Type
- single nucleotide variant
- Location
- chrX:134377740 (GRCh38)
- Structure
- AlphaFold pLDDT 73.45 · 2 PDB
- Residue 41
- the 'extended phd1 domain (ephd1)' region
Similar variants
- PHF6 p.Ala41Val Uncertain significance ★ ⚠ same residue
- PHF6 p.Arg225Ter Pathogenic ★★ same condition
- PHF6 p.Arg274Ter Pathogenic ★★ same condition
- PHF6 p.Arg166Lys Uncertain significance ★★ ⚠ same condition
- PHF6 p.Arg24Thr Uncertain significance ★★ ⚠ same condition
- PHF6 p.Gln114His Uncertain significance ★★ ⚠ same condition
- PHF6 p.Glu351Gly Uncertain significance ★★ ⚠ same condition
- PHF6 p.His43Arg 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-ala41 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown