TMEM151A p.Ser458=
c.1374C>T · VCV3770498
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.368%, nfe)
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 -0.91 | GERP -3.1, phastCons 0.002 |
| Overall | ||
| CADD | 9.083 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.368%
European (non-Finnish) · 4,222/1,147,810 alleles
Filtering AF
0.359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.355%
Overall
0.296%
4,571/1,544,654 alleles · rare
exomes 4,217/1,392,488 · genomes 354/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.368% | 272 |
| Amishnot grpmax-eligible | 0.329% | 304 |
| Remaining individualsnot grpmax-eligible | 0.173% | 579 |
| South Asian | 0.132% | 757 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0973% | 1,028 |
| African / African-American | 0.0657% | 1,523 |
| Finnishnot grpmax-eligible | 0.059% | 1,694 |
| Admixed American | 0.047% | 2,128 |
| Middle Eastern | 0.0182% | 5,486 |
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
- TMEM151A
- Protein
- p.Ser458=
- Coding
- c.1374C>T
- MANE Select
- NM_153266
- Type
- single nucleotide variant
- Location
- chr11:66295620 (GRCh38)
- Gene constraint
- LOEUF 1.322 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.63
- Residue 458
- a UniProt-annotated variant site (in ekd3); a UniProt-annotated variant site (in ekd3; uncertain significance)
Similar variants
- TMEM151A p.Pro276Leu Likely pathogenic ★ ⚠ same type
- TMEM151A p.Ala137Glu Uncertain significance ★ ⚠ same type
- TMEM151A p.Ala197Pro Uncertain significance ★ ⚠ same type
- TMEM151A p.Ala197Val Uncertain significance ★ ⚠ same type
- TMEM151A p.Ala211Val Uncertain significance ★ ⚠ same type
- TMEM151A p.Ala274Thr Uncertain significance ★ ⚠ same type
- TMEM151A p.Ala293Ser Uncertain significance ★ ⚠ same type
- TMEM151A p.Ala304Asp Uncertain significance ★ ⚠ same type
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/tmem151a-p-ser458 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown