DMRT1 p.Ala321=
c.963G>A · rs146258506 · VCV760726
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0255%, nfe)
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 -3.3 | |
| Overall | ||
| CADD | 0.606 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0255%
European (non-Finnish) · 301/1,180,042 alleles
Filtering AF
0.0231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0222%
Overall
0.0204%
330/1,614,050 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0255% | 3,920 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,207 |
| Middle Eastern | 0.0164% | 6,084 |
| Admixed American | 0.0117% | 8,571 |
| African / African-American | 0.00801% | 12,486 |
| South Asian | 0.0022% | 45,539 |
| Finnishnot grpmax-eligible | 0.00156% | 64,042 |
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
- DMRT1
- Protein
- p.Ala321=
- Coding
- c.963G>A
- MANE Select
- NM_021951
- dbSNP
- rs146258506
- Type
- single nucleotide variant
- Location
- chr9:916903 (GRCh38)
- Gene constraint
- LOEUF 0.432 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 57.76 · 1 PDB
- Residue 321
- the 'disordered' region
Similar variants
- DMRT1 p.Asn151Ser Uncertain significance ★★ ⚠ same type
- DMRT1 p.Met275Val Uncertain significance ★★ ⚠ same type
- DMRT1 p.Ser58Cys Uncertain significance ★★ ⚠ same type
- DMRT1 p.Thr366Ser Uncertain significance ★★ ⚠ same type
- DMRT1 p.Val265Met Uncertain significance ★★ ⚠ same type
- DMRT1 c.355-218G>C Benign ★★ same type
- DMRT1 c.355-8G>C Benign ★★ same type
- DMRT1 c.538+65A>G 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/dmrt1-p-ala321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown