TMEM231 p.Pro164=
c.492T>C · rs754580796 · VCV2939943
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000681%, nfe)
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 -1.4 | GERP -3.5 |
| Overall | ||
| CADD | 0.536 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000681%
European (non-Finnish) · 8/1,174,214 alleles
Filtering AF
0.000293%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000212%
Overall
0.000499%
8/1,603,780 alleles · very rare
exomes 7/1,454,896 · genomes 1/148,884 · 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
- TMEM231
- Protein
- p.Pro164=
- Coding
- c.492T>C
- MANE Select
- NM_001077418
- dbSNP
- rs754580796
- Type
- single nucleotide variant
- Location
- chr16:75545442 (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.Pro164Ser Uncertain significance ★★ ⚠ same residue
- TMEM231 p.Pro164Ala 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
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-pro164 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown