Is LEMD3 p.Glu450= (c.1350A>G) pathogenic?

LEMD3 p.Glu450= (c.1350A>G) is classified Benign/Likely benign in LEMD3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Rare (popmax 0.33%, mid); Associated with Buschke-Ollendorff syndrome.

What condition is associated with LEMD3 p.Glu450= (c.1350A>G)?

LEMD3 p.Glu450= (c.1350A>G) is associated with Buschke-Ollendorff syndrome (ClinVar).

How common is LEMD3 p.Glu450= (c.1350A>G) in the general population?

LEMD3 p.Glu450= (c.1350A>G) is rare (popmax 0.33%, mid) (gnomAD).

LEMD3 p.Glu450=

c.1350A>G · rs145116568 · VCV775098

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.33%, mid)

Conditions

Buschke-Ollendorff syndrome

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 2.3	GERP -1.3, phastCons 1
Overall
CADD	9.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.33% Middle Eastern · 20/6,062 alleles

Filtering AF 0.219% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.183%

Overall 0.0672% 1,085/1,614,218 alleles · rare exomes 989/1,461,888 · genomes 96/152,330 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.33%	303
Finnishnot grpmax-eligible	0.287%	348
Ashkenazi Jewishnot grpmax-eligible	0.233%	429
Remaining individualsnot grpmax-eligible	0.0896%	1,116
European (non-Finnish)	0.0597%	1,676
African / African-American	0.048%	2,085
Admixed American	0.0233%	4,288
South Asian	0.0022%	45,544

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: LEMD3
Protein: p.Glu450=
Coding: c.1350A>G
MANE Select: NM_014319
dbSNP: rs145116568
Type: single nucleotide variant
Location: chr12:65170946 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI 0.40 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.07 · 3 PDB

Full LEMD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Buschke-Ollendorff syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LEMD3 p.Arg678Ter Pathogenic/Likely pathogenic ★★ same condition
LEMD3 p.Glu601Ter Pathogenic/Likely pathogenic ★★ same condition
LEMD3 p.Ala127Val Uncertain significance ★★ ⚠ same condition
LEMD3 p.Asn257Asp Uncertain significance ★★ ⚠ same condition
LEMD3 p.Asn529Ser Uncertain significance ★★ ⚠ same condition
LEMD3 p.Asp214Tyr Uncertain significance ★★ ⚠ same condition
LEMD3 p.Asp544Ala Uncertain significance ★★ ⚠ same condition
LEMD3 p.Asp755Asn Uncertain significance ★★ ⚠ same condition

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/lemd3-p-glu450 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown