LETM1 p.Ser111=
c.333G>A · rs754403408 · VCV1625484
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -10 | GERP -5 |
| Overall | ||
| CADD | 0.249 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,006 alleles
Filtering AF
0.000542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000428%
Overall
0.000929%
15/1,614,044 alleles · very rare
exomes 14/1,461,890 · genomes 1/152,154 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,006 |
| African / African-American | 0.00133% | 74,920 |
| South Asian | 0.0011% | 91,086 |
| European (non-Finnish) | 0.00102% | 98,337 |
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.Ser111=
- Coding
- c.333G>A
- MANE Select
- NM_012318
- dbSNP
- rs754403408
- Type
- single nucleotide variant
- Location
- chr4:1841608 (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-ser111 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown