MADD p.Pro1067=
c.3201A>C · VCV4533834
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.377%, amr)
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 -1.4 | GERP -2.2 |
| Overall | ||
| CADD | 7.722 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.377%
Admixed American · 226/59,956 alleles
Filtering AF
0.337%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.321%
Overall
0.0148%
239/1,614,088 alleles · rare
exomes 207/1,461,788 · genomes 32/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.377% | 265 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,945 |
| African / African-American | 0.00533% | 18,760 |
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.Pro1067=
- Coding
- c.3201A>C
- MANE Select
- NM_001376571
- Type
- single nucleotide variant
- Location
- chr11:47290656 (GRCh38)
- Gene constraint
- LOEUF 0.725 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.59
- Residue 1067
- a UniProt-annotated variant site (in deeah; uncertain significance); a UniProt-annotated variant site (in deeah and neddish; uncertain significance); the 'disordered' region
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-pro1067 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown