ASPM p.Tyr462Ter
c.1386C>G · rs1553227742 · VCV520789
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 3 of 28 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.6 | GERP -0.86 |
| Overall | ||
| CADD | 20.7 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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
- ASPM
- Protein
- p.Tyr462Ter
- Coding
- c.1386C>G
- MANE Select
- NM_018136
- dbSNP
- rs1553227742
- Type
- single nucleotide variant
- Location
- chr1:197142866 (GRCh38)
- Gene constraint
- LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Similar variants
- ASPM p.Tyr462Cys Benign/Likely benign ★★ same residue
- ASPM p.Arg3304Ter Pathogenic ★★ same condition
- ASPM p.Arg3390Ter Pathogenic ★★ same condition
- ASPM p.Gln3060Ter Pathogenic ★★ same condition
- ASPM p.Gln3321Ter Pathogenic ★★ same condition
- ASPM p.Trp989Ter Pathogenic ★★ same condition
- ASPM p.Ala1125Val Uncertain significance ★★ ⚠ same condition
- ASPM p.Ala1319Ser Uncertain significance ★★ ⚠ same condition
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/aspm-p-tyr462ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown