TMEM237 p.Ala269=
c.807G>A · rs763452347 · VCV333561
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, amr)
Conditions
1
Joubert syndrome 14
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 -9.7 | GERP -5.6 |
| Overall | ||
| CADD | 4.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
Admixed American · 9/57,812 alleles
Filtering AF
0.0081%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00598%
Overall
0.000685%
11/1,606,982 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0156% | 6,424 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,122 |
| South Asian | 0.00112% | 89,280 |
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.Ala269=
- Coding
- c.807G>A
- MANE Select
- NM_001044385
- dbSNP
- rs763452347
- Type
- single nucleotide variant
- Location
- chr2:201629292 (GRCh38)
- Gene constraint
- LOEUF 1.318 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.79
Similar variants
- TMEM237 p.Ala269Val Uncertain significance ★★ ⚠ same residue
- 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
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-ala269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown