DLX6 p.Pro117Ser
c.349C>T · VCV3625175
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0268%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.282 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.3 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 1.24 | unconstrained · MANE · 1,662 bp · p 0.00049 · regional, not allelic |
| Overall | ||
| CADD | 22.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0268%
East Asian · 10/37,258 alleles
Filtering AF
0.0145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.011%
Overall
0.000878%
12/1,366,242 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0268% | 3,726 |
| Admixed American | 0.00208% | 48,106 |
| European (non-Finnish) | 8.85e-05% | 1,130,166 |
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
- DLX6
- Protein
- p.Pro117Ser
- Coding
- c.349C>T
- MANE Select
- NM_005222
- Type
- single nucleotide variant
- Location
- chr7:97006326 (GRCh38)
- Gene constraint
- LOEUF 0.379 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64
- Residue 117
- the 'disordered' region
Similar variants
- DLX6 p.Pro117_Tyr118insSer Uncertain significance ★ same residue
- DLX6 p.Ala82Val Uncertain significance ★★ same type
- DLX6 c.437-85A>C Benign ★★ same type
- DLX6 c.*9A>G Benign ★★ same type
- DLX6 p.Gln178= Benign ★★ same type
- DLX6 p.Gln35= Likely benign ★★ same type
- DLX6 p.Gln41= Likely benign ★★ same type
- DLX6 p.Pro282= Likely benign ★★ 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/dlx6-p-pro117ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown