ALS2 c.4004+34A>G
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +34 | near-intronic (+34 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.2 | GERP -3.3 |
| Non-coding constraint | Z 2.67 | 1 kb window · o/e 0.80 · regional · uncalibrated |
| Overall | ||
| CADD | 0.054 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,974 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.000682%
11/1,611,848 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 9,996 |
| European (non-Finnish) | 0.000424% | 235,633 |
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
- ALS2
- Coding
- c.4004+34A>G
- MANE Select
- NM_020919
- dbSNP
- rs746226743
- Type
- single nucleotide variant
- Location
- chr2:201715638 (GRCh38)
- Gene constraint
- LOEUF 0.649 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 74.69
Similar variants
- ALS2 c.1640+1G>A Pathogenic/Likely pathogenic ★★ same type
- ALS2 c.2580+2T>C Pathogenic ★★ same type
- ALS2 c.3703-2A>G Pathogenic/Likely pathogenic ★★ same type
- ALS2 c.4626+1G>A Pathogenic/Likely pathogenic ★★ same type
- ALS2 p.Ala573Glu Likely pathogenic ★★ same type
- ALS2 p.Arg1139Ter Pathogenic/Likely pathogenic ★★ same type
- ALS2 p.Arg1421Ter Pathogenic/Likely pathogenic ★★ same type
- ALS2 p.Arg1461Ter Pathogenic ★★ 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/als2-c-4004-plus-34a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown