LETM1 p.Arg27=
c.81G>A · rs528375844 · VCV787022
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.888%, afr)
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 -0.014 | GERP -1.5, phastCons 0.001 |
| Overall | ||
| CADD | 12.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.888%
African / African-American · 565/63,616 alleles
Filtering AF
0.828%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.803%
Overall
0.0495%
611/1,234,662 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.888% | 113 |
| Remaining individualsnot grpmax-eligible | 0.0738% | 1,356 |
| Admixed American | 0.0384% | 2,601 |
| South Asian | 0.0034% | 29,394 |
| European (non-Finnish) | 0.000303% | 330,338 |
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.Arg27=
- Coding
- c.81G>A
- MANE Select
- NM_012318
- dbSNP
- rs528375844
- Type
- single nucleotide variant
- Location
- chr4:1855870 (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-arg27 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown