Is LAMB3 p.Arg292= (c.876C>T) pathogenic?

LAMB3 p.Arg292= (c.876C>T) is classified Conflicting classifications of pathogenicity in LAMB3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-10-24). Very rare (popmax 0.000254%, nfe); Associated with junctional epidermolysis bullosa.

What condition is associated with LAMB3 p.Arg292= (c.876C>T)?

LAMB3 p.Arg292= (c.876C>T) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMB3 p.Arg292= (c.876C>T) in the general population?

LAMB3 p.Arg292= (c.876C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

LAMB3 p.Arg292=

c.876C>T · rs886045868 · VCV295125

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

junctional epidermolysis bullosa

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 4.5	GERP 1.1, phastCons 1
Overall
CADD	7.329	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,016 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,952 alleles · very rare exomes 2/1,461,868 · genomes 1/152,084 · joint denominator

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: LAMB3
Protein: p.Arg292=
Coding: c.876C>T
MANE Select: NM_000228
dbSNP: rs886045868
Type: single nucleotide variant
Location: chr1:209630682 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 292: the laminin egf-like 1 domain; a UniProt-annotated variant site (in)

Full LAMB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

junctional epidermolysis bullosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMB3 p.Arg292Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
LAMB3 c.1132+5G>A Pathogenic/Likely pathogenic ★★ same condition
LAMB3 c.1486-1G>A Likely pathogenic ★★ same condition
LAMB3 c.3228+1G>A Pathogenic ★★ same condition
LAMB3 c.565-2A>G Pathogenic ★★ same condition
LAMB3 c.628+1G>A Pathogenic/Likely pathogenic ★★ same condition
LAMB3 c.823-1G>A Pathogenic ★★ same condition
LAMB3 p.Arg144Ter Pathogenic ★★ 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/lamb3-p-arg292 (accessed [today's date]).

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