MADD p.Asp674=
c.2022C>T · VCV4911485
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0483%, sas)
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 -3.2 | GERP -4.6 |
| Overall | ||
| CADD | 6.653 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0483%
South Asian · 44/91,092 alleles
Filtering AF
0.0369%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.033%
Overall
0.00514%
83/1,613,970 alleles · ultra-rare
exomes 70/1,461,888 · genomes 13/152,082 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0483% | 2,070 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| European (non-Finnish) | 0.00271% | 36,876 |
| African / African-American | 0.00267% | 37,439 |
| Admixed American | 0.00167% | 59,988 |
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
- MADD
- Protein
- p.Asp674=
- Coding
- c.2022C>T
- MANE Select
- NM_001376571
- Type
- single nucleotide variant
- Location
- chr11:47284430 (GRCh38)
- Gene constraint
- LOEUF 0.725 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.59
- Residue 674
- a UniProt-annotated variant site (in deeah; uncertain significance); a UniProt-annotated variant site (in deeah and neddish; uncertain significance)
Similar variants
- MADD c.2816+1G>A Pathogenic ★★ same type
- MADD p.Arg1532Ter Pathogenic ★★ same type
- MADD p.Arg327Ter Pathogenic/Likely pathogenic ★★ same type
- MADD p.Ala1029Val Uncertain significance ★★ ⚠ same type
- MADD p.Ala165Val Uncertain significance ★★ ⚠ same type
- MADD p.Arg1077Gly Uncertain significance ★★ ⚠ same type
- MADD p.Arg1273His Uncertain significance ★★ ⚠ same type
- MADD p.Arg170His 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/madd-p-asp674 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown