DRP2 p.Ala453=
c.1359C>T · rs149586516 · VCV2995174
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.021%, afr)
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 0.14 | GERP -2.4, phastCons 0.94 |
| Overall | ||
| CADD | 6.702 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.021%
African / African-American · 12/57,132 alleles
Filtering AF
0.0121%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0095%
Overall
0.00157%
19/1,209,923 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.021% | 4,761 |
| South Asian | 0.0088% | 11,366 |
| Admixed American | 0.00219% | 45,757 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,589 |
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
- DRP2
- Protein
- p.Ala453=
- Coding
- c.1359C>T
- MANE Select
- NM_001197293 · reported on NM_001939
- dbSNP
- rs149586516
- Type
- single nucleotide variant
- Location
- chrX:101248195 (GRCh38)
- Structure
- AlphaFold pLDDT 90.49 · 15 PDB
- Residue 453
- a β-strand
Similar variants
- DRP2 p.Ala453Thr Uncertain significance ★ ⚠ same residue
- DRP2 p.Glu432Ter Pathogenic ★★ same type
- DPYSL2 p.Asn492Ser Uncertain significance ★★ ⚠ same type
- DPYSL2 p.Asp520Asn Uncertain significance ★★ ⚠ same type
- DRP2 p.Ala205Val Uncertain significance ★★ ⚠ same type
- DRP2 p.Ala643Thr Uncertain significance ★★ ⚠ same type
- DRP2 p.Arg199His Uncertain significance ★★ ⚠ same type
- DRP2 p.Arg224Cys 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/drp2-p-ala453 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown