ALS2CL p.Ser70=
c.210A>T · VCV4962100
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.354%, 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 -20 | GERP -3 |
| Overall | ||
| CADD | 0.401 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.354%
African / African-American · 266/75,038 alleles
Filtering AF
0.319%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.306%
Overall
0.018%
291/1,613,074 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.354% | 282 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,464 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.01% | 10,004 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000254% | 393,326 |
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
- ALS2CL
- Protein
- p.Ser70=
- Coding
- c.210A>T
- MANE Select
- NM_147129
- Type
- single nucleotide variant
- Location
- chr3:46688190 (GRCh38)
- Gene constraint
- LOEUF 1.08 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.50
Similar variants
- ALS2CL p.Ala207Ser Uncertain significance ★ ⚠ same type
- ALS2CL p.Ala212Thr Uncertain significance ★ ⚠ same type
- ALS2CL p.Ala343Thr Uncertain significance ★ ⚠ same type
- ALS2CL p.Ala35Val Uncertain significance ★ ⚠ same type
- ALS2CL p.Ala512Val Uncertain significance ★ ⚠ same type
- ALS2CL p.Ala701Thr Uncertain significance ★ ⚠ same type
- ALS2CL p.Ala713Thr Uncertain significance ★ ⚠ same type
- ALS2CL p.Arg11Trp 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/als2cl-p-ser70 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown