DISC1 p.Arg575Lys
c.1724G>A · rs202013247 · VCV2263931
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1966 | likely benign |
|---|---|---|
| REVEL | 0.339 | indeterminate |
| SaProt | LLR -6.59 | tolerated |
| ⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.7 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 1.05 | unconstrained · MANE · 266 kb · p 0.32 · regional, not allelic |
| Overall | ||
| CADD | 22.5 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.669% | 149 |
| Remaining individualsnot grpmax-eligible | 0.0448% | 2,230 |
| Admixed Americangrpmax | 0.0217% | 4,602 |
| European (non-Finnish) | 0.00322% | 31,043 |
| Finnishnot grpmax-eligible | 0.00159% | 62,754 |
| African / African-American | 0.00134% | 74,688 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg575Lys
- Coding
- c.1724G>A
- MANE Select
- NM_018662
- dbSNP
- rs202013247
- Type
- single nucleotide variant
- Location
- chr1:231800142 (GRCh38)
- Gene constraint
- LOEUF 0.893 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.74 · 1 PDB
- Residue 575
- 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-arg575lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown