DISC1 p.Ile452=
c.1356C>T · rs34268403 · VCV784975
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.947%, 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 0.22 | GERP 0.24 |
| Overall | ||
| CADD | 7.823 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.947%
African / African-American · 711/75,040 alleles
Filtering AF
0.89%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.867%
Overall
0.0486%
785/1,614,184 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.947% | 106 |
| Middle Eastern | 0.0825% | 1,212 |
| Remaining individualsnot grpmax-eligible | 0.0576% | 1,736 |
| Admixed American | 0.035% | 2,859 |
| South Asian | 0.0022% | 45,539 |
| European (non-Finnish) | 0.000847% | 118,004 |
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
- DISC1
- Protein
- p.Ile452=
- Coding
- c.1356C>T
- MANE Select
- NM_018662
- dbSNP
- rs34268403
- Type
- single nucleotide variant
- Location
- chr1:231767227 (GRCh38)
- Gene constraint
- LOEUF 0.893 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.74 · 1 PDB
- Residue 452
- the 'interaction with traf3ip1' region; the 'required for localization to punctate cytoplasmic foci' region; the 'necessary and sufficient for interaction with pcnt and localization at the centrosome' region
Similar variants
- DISC1 p.Cys187Tyr Uncertain significance ★★ ⚠ same type
- DISC1 p.Arg170Cys Benign ★★ same type
- DISC1 p.Arg345Gln Benign ★★ same type
- DISC1 p.Glu751Gln Benign ★★ same type
- DISC1 p.Leu330Phe Benign ★★ ⚠ same type
- DISC1 p.Pro432Leu Likely benign ★★ same type
- DISC1 p.Ala13Thr Uncertain significance ★ ⚠ same type
- DISC1 p.Ala220Val 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/disc1-p-ile452 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown