Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 83.2%, amr) — too common for a highly-penetrant pathogenic allele
Conditions
1
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome
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 -1.8, phastCons 1 |
| Overall | ||
| CADD | 6.739 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
83.2%
Admixed American · 49,044/58,938 alleles
Filtering AF
82.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 82.3%
Overall
70.9%
1,102,505/1,554,476 alleles · common
exomes 993,389/1,402,422 · genomes 109,116/152,054 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 83.2% | 1 |
| East Asian | 78.9% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 73.4% | 1 |
| Middle Eastern | 71.5% | 1 |
| Finnishnot grpmax-eligible | 71.1% | 1 |
| Remaining individualsnot grpmax-eligible | 71% | 1 |
| African / African-American | 70.9% | 1 |
| European (non-Finnish) | 70.2% | 1 |
| South Asian | 67% | 1 |
| Amishnot grpmax-eligible | 65.9% | 2 |
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
- SERAC1
- Protein
- p.Asp83=
- Coding
- c.249C>T
- MANE Select
- NM_032861
- dbSNP
- rs6929274
- Type
- single nucleotide variant
- Location
- chr6:158150469 (GRCh38)
- Gene constraint
- LOEUF 0.681 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.66
Disease context
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor MEGDEL syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- SERAC1 c.1403+1G>C Pathogenic ★★ same condition
- SERAC1 p.Arg148Ter Pathogenic ★★ same condition
- SERAC1 p.Arg368Ter Pathogenic ★★ same condition
- SERAC1 p.Arg387Ter Pathogenic/Likely pathogenic ★★ same condition
- SERAC1 p.Arg447Ter Pathogenic ★★ same condition
- SERAC1 p.Arg68Ter Pathogenic/Likely pathogenic ★★ same condition
- SERAC1 p.Gln376Ter Pathogenic ★★ same condition
- SERAC1 p.Ser498Thr Pathogenic/Likely pathogenic ★★ same condition
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/serac1-p-asp83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown