TMEM237 p.Ala116=
c.348G>A · rs191125006 · VCV198116
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 10 submitters
gnomAD v4.1
Rare
rare (popmax 0.374%, nfe)
Conditions
1
Joubert syndrome 14
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP -1.9, phastCons 0.44 |
| Overall | ||
| CADD | 10.76 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.374%
European (non-Finnish) · 4,377/1,170,524 alleles
Filtering AF
0.365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.361%
Overall
0.294%
4,694/1,595,414 alleles · rare
exomes 4,451/1,443,250 · genomes 243/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.374% | 267 |
| Remaining individualsnot grpmax-eligible | 0.249% | 402 |
| Admixed American | 0.12% | 836 |
| African / African-American | 0.067% | 1,492 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0651% | 1,537 |
| Middle Eastern | 0.0331% | 3,017 |
| Finnishnot grpmax-eligible | 0.0159% | 6,287 |
| South Asian | 0.0103% | 9,717 |
| East Asian | 0.00902% | 11,086 |
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.Ala116=
- Coding
- c.348G>A
- MANE Select
- NM_001044385
- dbSNP
- rs191125006
- Type
- single nucleotide variant
- Location
- chr2:201633358 (GRCh38)
- Gene constraint
- LOEUF 1.318 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.79
- Residue 116
- the 'disordered' region
Similar variants
- TMEM237 p.Ala116Thr Uncertain significance ★ ⚠ same residue
- TMEM237 p.Ala116Val 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
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-ala116 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown