ALG2 c.-36C>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.793%, 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 0.42 | phastCons 0.001 |
| Non-coding constraint | Z -1.63 | 1 kb window · o/e 1.10 · regional · uncalibrated |
| Overall | ||
| CADD | 5.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.793%
African / African-American · 586/73,876 alleles
Filtering AF
0.74%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.719%
Overall
0.0412%
638/1,546,746 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.793% | 126 |
| Remaining individualsnot grpmax-eligible | 0.0451% | 2,218 |
| Admixed American | 0.0293% | 3,408 |
| Middle Eastern | 0.0222% | 4,506 |
| South Asian | 0.00117% | 85,640 |
| European (non-Finnish) | 0.000608% | 164,362 |
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
- ALG2
- Coding
- c.-36C>A
- MANE Select
- NM_033087
- dbSNP
- rs185877575
- Type
- single nucleotide variant
- Location
- chr9:99221930 (GRCh38)
- Gene constraint
- LOEUF 1.408 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.03
Similar variants
- ALG2 c.348+568G>A Uncertain significance ★★ same type
- ALG2 p.Ala29Pro Uncertain significance ★★ ⚠ same type
- ALG2 p.Ala36Val Uncertain significance ★★ ⚠ same type
- ALG2 p.Ala71Gly Uncertain significance ★★ ⚠ same type
- ALG2 p.Ala71Val Uncertain significance ★★ ⚠ same type
- ALG2 p.Arg129Gln Uncertain significance ★★ ⚠ same type
- ALG2 p.Arg130Gln Uncertain significance ★★ ⚠ same type
- ALG2 p.Arg251His 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/alg2-c-minus-36c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown