TMEM237 p.Val246=
c.738G>A · rs199947989 · VCV257321
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00402%, afr)
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 0.46 | GERP -1, phastCons 0.99 |
| Overall | ||
| CADD | 10.08 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00402%
African / African-American · 3/74,708 alleles
Filtering AF
0.00307%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00329%
53/1,608,602 alleles · very rare
exomes 46/1,456,466 · genomes 7/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00402% | 24,903 |
| European (non-Finnish) | 0.00399% | 25,068 |
| Admixed American | 0.00341% | 29,305 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,268 |
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.Val246=
- Coding
- c.738G>A
- MANE Select
- NM_001044385
- dbSNP
- rs199947989
- Type
- single nucleotide variant
- Location
- chr2:201629361 (GRCh38)
- Gene constraint
- LOEUF 1.318 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.79
Similar variants
- TMEM237 p.Val246Met 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-val246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown