DISC1 p.Thr375=
c.1125G>A · VCV3840189
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, 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 -0.45 | GERP -2.9 |
| Overall | ||
| CADD | 5.765 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/75,028 alleles
Filtering AF
0.00623%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00467%
Overall
0.00112%
18/1,614,112 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,336 |
| East Asian | 0.00223% | 44,876 |
| South Asian | 0.0022% | 45,542 |
| Admixed American | 0.00167% | 60,002 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| European (non-Finnish) | 0.000339% | 295,004 |
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.Thr375=
- Coding
- c.1125G>A
- MANE Select
- NM_018662
- Type
- single nucleotide variant
- Location
- chr1:231749933 (GRCh38)
- Gene constraint
- LOEUF 0.893 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.74 · 1 PDB
- Residue 375
- the 'interaction with traf3ip1' region
Similar variants
- DISC1 p.Thr375Ser Uncertain significance ★ ⚠ same residue
- DISC1 p.Thr375Met Likely benign ★ same residue
- 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
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-thr375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown