CELF2 p.Ala409Thr
c.1225G>A · rs767822043 · VCV2365037
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1484 | likely benign |
|---|---|---|
| REVEL | 0.155 | moderately benign-leaning |
| SaProt | LLR -7.68 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 10 | GERP 2.7, phastCons 1 |
| Regional constraint | o/e 0.50 | unconstrained · MANE · 156 kb · p 7.3e-29 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | 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.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A396T vs ClinVar A409T) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.00957% | 10,451 |
| African / African-Americangrpmax | 0.00667% | 14,982 |
| Admixed American | 0.005% | 20,006 |
| European (non-Finnish) | 0.00322% | 31,053 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
| South Asian | 0.0011% | 91,086 |
Finnish 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
- CELF2
- Protein
- p.Ala409Thr
- Coding
- c.1225G>A
- MANE Select
- NM_001326342
- dbSNP
- rs767822043
- Type
- single nucleotide variant
- Location
- chr10:11321317 (GRCh38)
- Gene constraint
- LOEUF 0.294 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 66.26 · 7 PDB
- Residue 409
- the 'necessary for rna-binding, tnnt2 exon 5 and nmda r1 exon 21 inclusion' region
Similar variants
- CELF2 p.Arg506Cys Pathogenic/Likely pathogenic ★★ same type
- CELF2 p.Arg513His Likely pathogenic ★★ same type
- CELF2 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same type
- CELF2 p.Ala135Thr Uncertain significance ★★ ⚠ same type
- CELF2 p.Val95Leu Uncertain significance ★★ ⚠ same type
- CELF2 p.Arg506His Pathogenic ★ same type
- CELF2 p.Arg506Leu Pathogenic ★ same type
- CELF2 p.Arg513Cys Likely 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/celf2-p-ala409thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown