TMEM231 p.Pro59=
c.177G>C · rs78196225 · VCV130588
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.15%, afr)
Conditions
2
Meckel syndrome, type 11
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 0.037 | GERP 1.9, phastCons 0.85 |
| Overall | ||
| CADD | 13.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.15%
African / African-American · 3,099/74,734 alleles
Filtering AF
4.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.98%
Overall
0.228%
3,653/1,604,596 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.15% | 24 |
| Admixed American | 0.415% | 241 |
| Remaining individualsnot grpmax-eligible | 0.312% | 320 |
| Middle Eastern | 0.198% | 504 |
| South Asian | 0.0135% | 7,434 |
| European (non-Finnish) | 0.00765% | 13,068 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00683% | 14,634 |
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.Pro59=
- Coding
- c.177G>C
- MANE Select
- NM_001077418
- dbSNP
- rs78196225
- Type
- single nucleotide variant
- Location
- chr16:75555936 (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.Pro59Ala Uncertain significance ★★ ⚠ same residue
- TMEM231 p.Pro59Gln 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-pro59 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown