CELSR2 p.Val2171Ile
c.6511G>A · rs760959194 · VCV1918499
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1007 | likely benign |
|---|---|---|
| REVEL | 0.073 | moderately benign-leaning |
| SaProt | — | not scored · why |
| ⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.6, phastCons 1 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 15 kb · p 2.9e-09 · regional, not allelic |
| Overall | ||
| CADD | 22.8 | 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 is an independent agreement signal.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0501% | 1,998 |
| Remaining individualsnot grpmax-eligible | 0.00482% | 20,747 |
| East Asiangrpmax | 0.00447% | 22,367 |
| African / African-American | 0.00267% | 37,430 |
| South Asian | 0.0022% | 45,409 |
| European (non-Finnish) | 0.00161% | 61,933 |
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
- CELSR2
- Protein
- p.Val2171Ile
- Coding
- c.6511G>A
- MANE Select
- NM_001408
- dbSNP
- rs760959194
- Type
- single nucleotide variant
- Location
- chr1:109268888 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
Similar variants
- CELSR2 c.8338+1G>C Uncertain significance ★★ same type
- CELSR2 p.Ala1114Val Uncertain significance ★★ ⚠ same type
- CELSR2 p.Ala2145Thr Uncertain significance ★★ ⚠ same type
- CELSR2 p.Ala2574Thr Uncertain significance ★★ ⚠ same type
- CELSR2 p.Arg1171Gln Uncertain significance ★★ ⚠ same type
- CELSR2 p.Arg1328His Uncertain significance ★★ ⚠ same type
- CELSR2 p.Arg1400His Uncertain significance ★★ same type
- CELSR2 p.Arg1978Gln 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/celsr2-p-val2171ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown