LMOD2 p.Pro433del
c.1278TCC[4] · VCV4897659
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.309%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -4.2, phastCons 0.004 |
| Overall | ||
| CADD | 0.964 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | (CCT)n simple repeat · ambiguous alignment · confidence, not pathogenicity |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.309%
African / African-American · 224/72,408 alleles
Filtering AF
0.276%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.263%
Overall
0.065%
993/1,527,562 alleles · rare
exomes 883/1,377,804 · genomes 110/149,758 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.309% | 323 |
| Admixed American | 0.0954% | 1,048 |
| South Asian | 0.0699% | 1,430 |
| Remaining individualsnot grpmax-eligible | 0.0528% | 1,893 |
| European (non-Finnish) | 0.0516% | 1,937 |
| East Asian | 0.0418% | 2,391 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0399% | 2,504 |
| Finnishnot grpmax-eligible | 0.0294% | 3,407 |
| Middle Eastern | 0.0217% | 4,602 |
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
- LMOD2
- Protein
- p.Pro433del
- Coding
- c.1278TCC[4]
- MANE Select
- NM_207163
- Type
- Microsatellite
- Location
- chr7:123662862 (GRCh38)
- Gene constraint
- LOEUF 0.984 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.14 · 6 PDB
- Residue 433
- a UniProt-annotated variant site (in cmd2g; no protein detected by western blot in cardiac tissue from a homozygous patient); the 'interaction with actin 2' region; the 'disordered' region
Similar variants
- LMOD2 p.Asn325fs Likely pathogenic ★ same type
- LMOD2 p.Leu415fs Pathogenic 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/lmod2-p-pro433del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown