Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 8.53%, eas) — too common for a highly-penetrant pathogenic allele
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 1.1 | GERP 0.81, phastCons 1 |
| Overall | ||
| CADD | 8.114 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.53%
East Asian · 3,823/44,830 alleles
Filtering AF
8.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.21%
Overall
0.374%
6,030/1,613,168 alleles · common
exomes 5,482/1,460,904 · genomes 548/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 8.53% | 12 |
| Admixed American | 1.61% | 62 |
| Remaining individualsnot grpmax-eligible | 0.411% | 243 |
| South Asian | 0.326% | 307 |
| Ashkenazi Jewishnot grpmax-eligible | 0.321% | 311 |
| Middle Eastern | 0.231% | 432 |
| European (non-Finnish) | 0.0472% | 2,118 |
| African / African-American | 0.0293% | 3,409 |
| Finnishnot grpmax-eligible | 0.00156% | 63,978 |
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
- DTX4
- Protein
- p.Val355=
- Coding
- c.1065C>T
- MANE Select
- NM_015177
- dbSNP
- rs2275991
- Type
- single nucleotide variant
- Location
- chr11:59189229 (GRCh38)
- Gene constraint
- LOEUF 0.732 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.83
Similar variants
- DTX4 p.Ala342= Benign ★★ same type
- DTX4 p.Thr284= Benign ★★ same type
- DTX4 p.Val257Gly Benign ★★ same type
- DTX4 p.Ala171Thr Uncertain significance ★ ⚠ same type
- DTX4 p.Ala288Pro Uncertain significance ★ ⚠ same type
- DTX4 p.Ala303Gly Uncertain significance ★ ⚠ same type
- DTX4 p.Ala310Thr Uncertain significance ★ ⚠ same type
- DTX4 p.Ala40Gly 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/dtx4-p-val355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown