Is LAMB3 p.Lys188fs (c.561del) pathogenic?

LAMB3 p.Lys188fs (c.561del) is classified Likely pathogenic in LAMB3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-06-13). No allele count reported in gnomAD v4.1 (AN 1,613,660); Associated with junctional epidermolysis bullosa Herlitz type.

What condition is associated with LAMB3 p.Lys188fs (c.561del)?

LAMB3 p.Lys188fs (c.561del) is associated with junctional epidermolysis bullosa Herlitz type (ClinVar).

How common is LAMB3 p.Lys188fs (c.561del) in the general population?

LAMB3 p.Lys188fs (c.561del) is no allele count reported in gnomAD v4.1 (AN 1,613,660) (gnomAD).

LAMB3 p.Lys188fs

Q: How is Severe generalized junctional epidermolysis bullosa inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.561del · rs1057516947 · VCV371026

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,660)

Conditions

junctional epidermolysis bullosa Herlitz type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,660). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LAMB3
Protein: p.Lys188fs
Coding: c.561del
MANE Select: NM_000228
dbSNP: rs1057516947
Type: Deletion
Location: chr1:209634450 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 188: the laminin n-terminal domain

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

Disease context

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

For Severe generalized junctional epidermolysis bullosa (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

LAMB3 c.2911_2938del Pathogenic/Likely pathogenic ★★ same condition
LAMB3 p.Ala1055fs Pathogenic/Likely pathogenic ★★ same condition
LAMB3 p.Ala832fs Pathogenic/Likely pathogenic ★★ same condition
LAMB3 p.Asn456fs Pathogenic/Likely pathogenic ★★ same condition
LAMB3 p.Cys453fs Pathogenic/Likely pathogenic ★★ same condition
LAMB3 p.Cys788fs Pathogenic/Likely pathogenic ★★ same condition
LAMB3 p.Gly530fs Pathogenic ★★ same condition
LAMB3 p.Gly558_Leu559insTer Pathogenic/Likely 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-lys188fs (accessed [today's date]).

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