LRMDA p.Leu74=
c.222A>G · rs112676064 · VCV730707
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.58%, 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 6.1 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 6.599 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.58%
African / African-American · 1,182/74,978 alleles
Filtering AF
1.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.47%
Overall
0.0828%
1,337/1,614,002 alleles · low-frequency
exomes 632/1,461,844 · genomes 705/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.58% | 63 |
| Remaining individualsnot grpmax-eligible | 0.11% | 906 |
| Admixed American | 0.0933% | 1,072 |
| Middle Eastern | 0.0664% | 1,507 |
| South Asian | 0.0132% | 7,589 |
| European (non-Finnish) | 0.00119% | 84,286 |
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
- LRMDA
- Protein
- p.Leu74=
- Coding
- c.222A>G
- MANE Select
- NM_001305581
- dbSNP
- rs112676064
- Type
- single nucleotide variant
- Location
- chr10:76036098 (GRCh38)
- Gene constraint
- LOEUF 0.958 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.40
Similar variants
- LRMDA p.Arg184Cys Uncertain significance ★★ ⚠ same type
- LRMDA p.Arg207His Uncertain significance ★★ ⚠ same type
- LRMDA p.Met166Thr Uncertain significance ★★ ⚠ same type
- LRMDA p.Tyr129Cys Uncertain significance ★★ ⚠ same type
- LRMDA c.132-253009C>T Benign/Likely benign ★★ same type
- LRMDA c.398+31A>C Benign ★★ same type
- LRMDA c.516+53C>T Benign ★★ same type
- LRMDA c.601+18T>G Likely benign ★★ 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/lrmda-p-leu74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown