ALS2 c.2979+5G>A
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000255%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +5 | donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.64 | donor loss, 5 bp away · masked 0 · deltas |
| Pangolin | Δ0.77 | loss · gain 0.04 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.6, phastCons 1 |
| Non-coding constraint | Z 2.93 | 1 kb window · o/e 0.79 · regional · uncalibrated |
| Overall | ||
| CADD | 19.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000255%
European (non-Finnish) · 3/1,175,840 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000206%
3/1,457,304 alleles · very rare
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.2979+5G>A
- MANE Select
- NM_020919
- dbSNP
- rs1553506071
- Type
- single nucleotide variant
- Location
- chr2:201727207 (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-2979-plus-5g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown