LETM1 p.Val93=
c.279G>A · VCV3711420
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.247%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.57 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4 | GERP -4.5 |
| Overall | ||
| CADD | 13.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.247%
Middle Eastern · 15/6,062 alleles
Filtering AF
0.152%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.123%
Overall
0.00235%
38/1,614,198 alleles · rare
exomes 32/1,461,892 · genomes 6/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.247% | 404 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,418 |
| African / African-American | 0.00933% | 10,720 |
| European (non-Finnish) | 0.000847% | 118,004 |
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
- LETM1
- Protein
- p.Val93=
- Coding
- c.279G>A
- MANE Select
- NM_012318
- Type
- single nucleotide variant
- Location
- chr4:1841662 (GRCh38)
- Gene constraint
- LOEUF 0.881 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.36 · 2 PDB
Similar variants
- LETM1 p.Ala178Val Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg106His Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg112Cys Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg156Gln Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg307Cys Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg307His Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg323Gln Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg351Gln 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/letm1-p-val93 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown