DTHD1 p.Leu565=
c.1695G>A · rs1206153139 · VCV1543202
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.022%, 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 2.4 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 4.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.022%
East Asian · 9/40,906 alleles
Filtering AF
0.0114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00855%
Overall
0.000644%
10/1,551,870 alleles · ultra-rare
exomes 10/1,399,550 · genomes 0/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.022% | 4,545 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,170 |
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
- DTHD1
- Protein
- p.Leu565=
- Coding
- c.1695G>A
- MANE Select
- NM_001170700
- dbSNP
- rs1206153139
- Type
- single nucleotide variant
- Location
- chr4:36306242 (GRCh38)
- Gene constraint
- LOEUF 1.034 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.99
Similar variants
- DTHD1 c.1218+1G>A Uncertain significance ★★ same type
- DTHD1 c.1219-2A>G Uncertain significance ★★ same type
- DTHD1 p.Ala552Ser Uncertain significance ★★ ⚠ same type
- DTHD1 p.Ala811Asp Uncertain significance ★★ ⚠ same type
- DTHD1 p.Arg326Gln Uncertain significance ★★ ⚠ same type
- DTHD1 p.Arg371Cys Uncertain significance ★★ ⚠ same type
- DTHD1 p.Arg447Gln Uncertain significance ★★ ⚠ same type
- DTHD1 p.Arg447Ter 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/dthd1-p-leu565 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown