DLX4 p.Pro199=
c.597A>C · rs1598148629 · VCV3025586
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0233%, eas)
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 1 | GERP -1, phastCons 0.025 |
| Overall | ||
| CADD | 8.194 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0233%
East Asian · 10/42,996 alleles
Filtering AF
0.0126%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00952%
Overall
0.00798%
125/1,566,548 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0233% | 4,300 |
| Finnishnot grpmax-eligible | 0.0199% | 5,031 |
| Remaining individualsnot grpmax-eligible | 0.0132% | 7,563 |
| South Asian | 0.00787% | 12,706 |
| European (non-Finnish) | 0.00724% | 13,811 |
| African / African-American | 0.00409% | 24,429 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00347% | 28,860 |
| Admixed American | 0.00171% | 58,438 |
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
- DLX4
- Protein
- p.Pro199=
- Coding
- c.597A>C
- MANE Select
- NM_138281
- dbSNP
- rs1598148629
- Type
- single nucleotide variant
- Location
- chr17:49973817 (GRCh38)
- Gene constraint
- LOEUF 1.056 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.80
Similar variants
- DLX4 p.Pro199Leu Uncertain significance ★ ⚠ same residue
- DLX4 p.Ala77Thr Uncertain significance ★★ ⚠ same type
- DLX4 p.Leu201His Uncertain significance ★★ ⚠ same type
- DLX4 p.Ser203Thr Uncertain significance ★★ ⚠ same type
- DLX4 p.Ala94= Likely benign ★★ same type
- DLX4 p.Arg135Pro Likely benign ★★ same type
- DLX4 p.Ser68= Benign/Likely benign ★★ same type
- DLX4 p.Ala143Val 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/dlx4-p-pro199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown