DTX1 p.Pro277=
c.831A>G · rs972390216 · VCV2643346
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0412%, mid)
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 -1.2 | GERP -2.4 |
| Overall | ||
| CADD | 1.298 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0412%
Middle Eastern · 1/2,428 alleles
Filtering AF
0.00663%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0061%
Overall
0.0084%
91/1,083,494 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0412% | 2,428 |
| East Asian | 0.0161% | 6,207 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,893 |
| Admixed American | 0.0107% | 9,336 |
| South Asian | 0.00869% | 11,503 |
| African / African-American | 0.00848% | 11,789 |
| European (non-Finnish) | 0.00816% | 12,248 |
| Finnishnot grpmax-eligible | 0.00517% | 19,326 |
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
- DTX1
- Protein
- p.Pro277=
- Coding
- c.831A>G
- MANE Select
- NM_004416
- dbSNP
- rs972390216
- Type
- single nucleotide variant
- Location
- chr12:113077995 (GRCh38)
- Gene constraint
- LOEUF 0.74 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.10 · 5 PDB
- Residue 277
- the 'disordered' region
Similar variants
- DTX1 p.Gly445Asp Uncertain significance ★★ ⚠ same type
- DTX1 p.Ser101= Benign ★★ same type
- DTX1 p.Ala226Glu Uncertain significance ★ ⚠ same type
- DTX1 p.Ala226Thr Uncertain significance ★ ⚠ same type
- DTX1 p.Ala256Ser Uncertain significance ★ ⚠ same type
- DTX1 p.Ala260Val Uncertain significance ★ ⚠ same type
- DTX1 p.Ala267Pro Uncertain significance ★ ⚠ same type
- DTX1 p.Ala275Val 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/dtx1-p-pro277 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown