DIP2A p.Asp458=
c.1374C>T · rs531974273 · VCV749967
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, 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 -13 | GERP -4.2 |
| Overall | ||
| CADD | 2.026 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.00316%
51/1,614,030 alleles · ultra-rare
exomes 48/1,461,698 · genomes 3/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| South Asian | 0.00769% | 13,012 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| European (non-Finnish) | 0.00339% | 29,497 |
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
- DIP2A
- Protein
- p.Asp458=
- Coding
- c.1374C>T
- MANE Select
- NM_015151
- dbSNP
- rs531974273
- Type
- single nucleotide variant
- Location
- chr21:46533592 (GRCh38)
- Gene constraint
- LOEUF 0.617 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.93
Similar variants
- DIP2A p.Ala676Thr Uncertain significance ★★ ⚠ same type
- DIP2A p.Glu832Lys Uncertain significance ★★ ⚠ same type
- DIP2A p.Pro333= Benign ★★ same type
- DIP2A p.Pro798Leu Benign/Likely benign ★★ same type
- DIP2A p.Thr848= Benign/Likely benign ★★ same type
- DIP2A p.Val1531= Benign ★★ same type
- DIP2A c.1429+2T>G Likely pathogenic ★ same type
- DIP2A c.2395-2A>G 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/dip2a-p-asp458 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown