LETM1 p.Pro324=
c.972G>A · rs750387749 · VCV2173058
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0335%, mid)
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 -16 | GERP -3.8 |
| Overall | ||
| CADD | 8.352 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0335%
Middle Eastern · 2/5,970 alleles
Filtering AF
0.0059%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00245%
Overall
0.000929%
15/1,613,840 alleles · ultra-rare
exomes 14/1,461,688 · genomes 1/152,152 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0335% | 2,985 |
| African / African-American | 0.00801% | 12,481 |
| East Asian | 0.00223% | 44,894 |
| South Asian | 0.0022% | 45,533 |
| European (non-Finnish) | 0.000339% | 294,999 |
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.Pro324=
- Coding
- c.972G>A
- MANE Select
- NM_012318
- dbSNP
- rs750387749
- Type
- single nucleotide variant
- Location
- chr4:1832852 (GRCh38)
- Gene constraint
- LOEUF 0.881 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.36 · 2 PDB
- Residue 324
- the letm1 rbd domain
Similar variants
- LETM1 p.Pro324Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro324 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown