ADSS2 p.Ala417=
c.1251G>A · VCV4246465
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
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 -8 | GERP -4.2 |
| Overall | ||
| CADD | 2.868 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/59,998 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.00198%
32/1,613,796 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 6,000 |
| South Asian | 0.0022% | 45,515 |
| Finnishnot grpmax-eligible | 0.00156% | 63,998 |
| European (non-Finnish) | 0.00153% | 65,546 |
| African / African-American | 0.00133% | 75,030 |
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
- ADSS2
- Protein
- p.Ala417=
- Coding
- c.1251G>A
- MANE Select
- NM_001126
- Type
- single nucleotide variant
- Location
- chr1:244411354 (GRCh38)
- Gene constraint
- LOEUF 0.646 · pLI 0.14 (gnomAD)
- Structure
- AlphaFold pLDDT 92.90 · 1 PDB
Similar variants
- ADSS2 p.Ala417Ser Uncertain significance ★ ⚠ same residue
- ADSS2 p.Ala417Val Uncertain significance ★ ⚠ same residue
- ADSS2 p.Ala349Thr Uncertain significance ★ ⚠ same type
- ADSS2 p.Ala390Val Uncertain significance ★ ⚠ same type
- ADSS2 p.Asn409Lys Uncertain significance ★ ⚠ same type
- ADSS2 p.Asn90Lys Uncertain significance ★ ⚠ same type
- ADSS2 p.Asp17Asn Uncertain significance ★ ⚠ same type
- ADSS2 p.Asp381Asn 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/adss2-p-ala417 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown