TMEM231 p.Val152=
c.456G>A · rs571562822 · VCV729505
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0351%, mid)
Conditions
2
Joubert syndrome 20
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 4 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 10.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0351%
Middle Eastern · 2/5,706 alleles
Filtering AF
0.0122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00933%
Overall
0.00159%
25/1,574,174 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0351% | 2,853 |
| East Asian | 0.0227% | 4,397 |
| Remaining individualsnot grpmax-eligible | 0.00493% | 20,291 |
| European (non-Finnish) | 0.000864% | 115,702 |
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
- TMEM231
- Protein
- p.Val152=
- Coding
- c.456G>A
- MANE Select
- NM_001077418
- dbSNP
- rs571562822
- Type
- single nucleotide variant
- Location
- chr16:75545478 (GRCh38)
- Gene constraint
- LOEUF 1.41 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 88.65
Similar variants
- TMEM231 p.Val152Met Uncertain significance ★★ ⚠ same residue
- TMEM231 c.139+47C>A Pathogenic/Likely pathogenic ★★ same condition
- TMEM231 c.438+1G>A Pathogenic ★★ same condition
- TMEM231 c.438+1G>C Pathogenic/Likely pathogenic ★★ same condition
- TMEM231 c.582+1G>A Pathogenic/Likely pathogenic ★★ same condition
- TMEM231 p.Ala2Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- TMEM231 p.Ala42Thr Pathogenic/Likely pathogenic ★★ same condition
- TMEM231 p.Arg192Ter 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/tmem231-p-val152 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown