TMEM237 p.Ala19=
c.57T>C · VCV4823226
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000171%, nfe)
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 -0.17 | GERP -4.2, phastCons 0.042 |
| Overall | ||
| CADD | 7.51 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000171%
European (non-Finnish) · 2/1,171,744 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000125%
2/1,602,520 alleles · very rare
exomes 2/1,450,194 · genomes 0/152,326 · joint denominator
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.Ala19=
- Coding
- c.57T>C
- MANE Select
- NM_001044385
- Type
- single nucleotide variant
- Location
- chr2:201640910 (GRCh38)
- Gene constraint
- LOEUF 1.318 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.79
- Residue 19
- the 'disordered' region
Similar variants
- TMEM237 p.Ala19Gly Uncertain significance ★ ⚠ same residue
- TMEM237 c.136+1G>T Likely pathogenic ★★ same type
- TMEM237 c.553+1G>A Pathogenic/Likely pathogenic ★★ same type
- TMEM237 c.677+1G>A Pathogenic/Likely pathogenic ★★ same type
- TMEM237 c.869+1G>A Pathogenic/Likely pathogenic ★★ same type
- TMEM237 c.943+1G>T Pathogenic ★★ same type
- TMEM237 p.Arg109Ter Pathogenic ★★ same type
- TMEM237 p.Arg18Ter 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/tmem237-p-ala19 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown