TMEM231 p.Pro166=
c.498G>A · rs201636741 · VCV385987
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.45%, afr)
Conditions
2
Meckel syndrome, type 11
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.76 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.34 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.5 |
| Overall | ||
| CADD | 13.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.45%
African / African-American · 1,065/73,678 alleles
Filtering AF
1.37%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.34%
Overall
0.082%
1,316/1,605,626 alleles · low-frequency
exomes 678/1,456,414 · genomes 638/149,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.45% | 69 |
| Admixed American | 0.194% | 514 |
| Remaining individualsnot grpmax-eligible | 0.122% | 818 |
| Middle Eastern | 0.1% | 995 |
| Ashkenazi Jewishnot grpmax-eligible | 0.017% | 5,893 |
| South Asian | 0.00774% | 12,925 |
| European (non-Finnish) | 0.00357% | 27,988 |
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.Pro166=
- Coding
- c.498G>A
- MANE Select
- NM_001077418
- dbSNP
- rs201636741
- Type
- single nucleotide variant
- Location
- chr16:75545436 (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.Pro166Ala Uncertain significance ★ ⚠ same residue
- TMEM231 p.Pro166Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- TMEM231 p.Pro166Arg 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
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-pro166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown