ASPM p.Ser3219=
c.9657T>G · rs756879923 · VCV289606
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0861%, mid)
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 -0.2 | GERP 0.3, phastCons 0.001 |
| Overall | ||
| CADD | 5.383 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0861%
Middle Eastern · 5/5,806 alleles
Filtering AF
0.0338%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.022%
Overall
0.0054%
87/1,610,406 alleles · ultra-rare
exomes 79/1,458,322 · genomes 8/152,084 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0861% | 1,161 |
| Admixed American | 0.015% | 6,651 |
| Remaining individualsnot grpmax-eligible | 0.00963% | 10,383 |
| European (non-Finnish) | 0.0056% | 17,846 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,536 |
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.Ser3219=
- Coding
- c.9657T>G
- MANE Select
- NM_018136
- dbSNP
- rs756879923
- Type
- single nucleotide variant
- Location
- chr1:197090368 (GRCh38)
- Gene constraint
- LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 3219
- the iq 39 domain
Similar variants
- 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
- ASPM p.Arg1271Ter Pathogenic ★★ same type
- ASPM p.Arg1392Ter 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-ser3219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown