ADSL p.Ser151Arg
c.453T>G · VCV3907844
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.2806 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2806 | likely benign ⚠ discordant with ClinVar |
|---|---|---|
| REVEL | 0.309 | indeterminate |
| SaProt | LLR -8.16 | tolerated |
| ⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.54 | GERP -2.1 |
| Regional constraint | o/e 0.79 | unconstrained · MANE · 20 kb · p 5.6e-07 · regional, not allelic |
| Overall | ||
| CADD | 16.06 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ADSL
- Protein
- p.Ser151Arg
- Coding
- c.453T>G
- MANE Select
- NM_000026
- Type
- single nucleotide variant
- Location
- chr22:40354298 (GRCh38)
- Gene constraint
- LOEUF 0.915 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.82 · 4 PDB
- Residue 151
- a turn
Similar variants
- ADSL p.Ser151Gly Uncertain significance ★ ⚠ same residue
- ADSL c.1191+5G>C Pathogenic/Likely pathogenic ★★ same type
- ADSL c.402+1G>T Likely pathogenic ★★ same type
- ADSL c.482+1G>C Likely pathogenic ★★ same type
- ADSL c.-49T>C Pathogenic/Likely pathogenic ★★ same type
- ADSL p.Arg141Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- ADSL p.Arg149Ter Pathogenic/Likely pathogenic ★★ same type
- ADSL p.Arg190Gln Pathogenic/Likely 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/adsl-p-ser151arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown