ASPM p.Pro998=
c.2994G>A · rs554545885 · VCV290410
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0253%, 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 -0.24 | GERP -3.4, phastCons 0.001 |
| Overall | ||
| CADD | 5.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0253%
African / African-American · 19/74,978 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00248%
40/1,613,916 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0253% | 3,946 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,832 |
| East Asian | 0.00446% | 22,420 |
| Admixed American | 0.00167% | 60,014 |
| European (non-Finnish) | 0.00119% | 84,280 |
| South Asian | 0.0011% | 91,078 |
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
- ASPM
- Protein
- p.Pro998=
- Coding
- c.2994G>A
- MANE Select
- NM_018136
- dbSNP
- rs554545885
- Type
- single nucleotide variant
- Location
- chr1:197125134 (GRCh38)
- Gene constraint
- LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 998
- the calponin-homology (ch) 1 domain
Similar variants
- ASPM p.Pro998Leu Uncertain significance ★ ⚠ same residue
- ASPM p.Pro998Ser Uncertain significance ★ ⚠ same residue
- ASPM c.2419+2T>C Pathogenic/Likely pathogenic ★★ same type
- ASPM c.2488-1G>C Pathogenic/Likely pathogenic ★★ same type
- ASPM c.2936+5G>A Likely pathogenic ★★ same type
- ASPM c.3082+1G>C Pathogenic/Likely pathogenic ★★ same type
- ASPM c.9084+5G>A Likely pathogenic ★★ same type
- ASPM p.Arg1019Ter 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/aspm-p-pro998 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown