Is LAMB3 p.Val753fs (c.2257_2258insGCCACAAGCT) pathogenic?

LAMB3 p.Val753fs (c.22572258insGCCACAAGCT) is classified Likely pathogenic in LAMB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-14). Absent from gnomAD; Associated with junctional epidermolysis bullosa.

What condition is associated with LAMB3 p.Val753fs (c.2257_2258insGCCACAAGCT)?

LAMB3 p.Val753fs (c.2257_2258insGCCACAAGCT) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMB3 p.Val753fs (c.2257_2258insGCCACAAGCT) in the general population?

LAMB3 p.Val753fs (c.2257_2258insGCCACAAGCT) is absent from gnomAD (gnomAD).

LAMB3 p.Val753fs

c.2257_2258insGCCACAAGCT · rs2464797493 · VCV1725177

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

junctional epidermolysis bullosa

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 16 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.14	GERP -2.8

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Val753fs
Coding: c.2257_2258insGCCACAAGCT
MANE Select: NM_000228
dbSNP: rs2464797493
Type: Insertion
Location: chr1:209623605 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 753: the 'domain ii' region

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.Thr285fs Likely pathogenic ★ same condition
LAMB3 p.Val753= Likely benign ★ same residue
LAMB3 c.1132+5G>A Pathogenic/Likely pathogenic ★★ same condition
LAMB3 c.1486-1G>A Likely pathogenic ★★ same condition
LAMB3 c.2685_2701+2del 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

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-val753fs (accessed [today's date]).

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