Is LEMD3 p.Val94= (c.282C>G) pathogenic?

LEMD3 p.Val94= (c.282C>G) is classified Conflicting classifications of pathogenicity in LEMD3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-28). Rare (popmax 0.164%, mid); Associated with Buschke-Ollendorff syndrome.

What condition is associated with LEMD3 p.Val94= (c.282C>G)?

LEMD3 p.Val94= (c.282C>G) is associated with Buschke-Ollendorff syndrome (ClinVar).

How common is LEMD3 p.Val94= (c.282C>G) in the general population?

LEMD3 p.Val94= (c.282C>G) is rare (popmax 0.164%, mid) (gnomAD).

LEMD3 p.Val94=

c.282C>G · rs867412512 · VCV289423

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.164%, mid)

Conditions

Buschke-Ollendorff syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	6.602	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.164% Middle Eastern · 8/4,880 alleles

Filtering AF 0.0815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0595%

Overall 0.00764% 111/1,452,422 alleles · rare exomes 97/1,300,388 · genomes 14/152,034 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.164%	610
East Asian	0.0127%	7,866
Remaining individualsnot grpmax-eligible	0.0108%	9,262
European (non-Finnish)	0.00789%	12,669
South Asian	0.00293%	34,106
African / African-American	0.00289%	34,560
Admixed American	0.00285%	35,076

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.Val94=
Coding: c.282C>G
MANE Select: NM_014319
dbSNP: rs867412512
Type: single nucleotide variant
Location: chr12:65169878 (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-val94 (accessed [today's date]).

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