TMEM237 p.Val394=
c.1182G>A · VCV3585220
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
Joubert syndrome 14
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | acceptor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.76 | phastCons 1 |
| Overall | ||
| CADD | 7.243 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,942 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000248%
4/1,612,294 alleles · very rare
exomes 4/1,460,092 · genomes 0/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,942 |
| European (non-Finnish) | 0.000254% | 393,005 |
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
- TMEM237
- Protein
- p.Val394=
- Coding
- c.1182G>A
- MANE Select
- NM_001044385
- Type
- single nucleotide variant
- Location
- chr2:201624300 (GRCh38)
- Gene constraint
- LOEUF 1.318 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.79
Similar variants
- TMEM237 c.136+1G>T Likely pathogenic ★★ same condition
- TMEM237 c.553+1G>A Pathogenic/Likely pathogenic ★★ same condition
- TMEM237 c.677+1G>A Pathogenic/Likely pathogenic ★★ same condition
- TMEM237 c.869+1G>A Pathogenic/Likely pathogenic ★★ same condition
- TMEM237 c.943+1G>T Pathogenic ★★ same condition
- TMEM237 p.Arg109Ter Pathogenic ★★ same condition
- TMEM237 p.Arg18Ter Pathogenic ★★ same condition
- TMEM237 p.Arg301Ter Pathogenic/Likely pathogenic ★★ same condition
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/tmem237-p-val394 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown