Is LAMB3 p.Ser155fs (c.463dup) pathogenic?

LAMB3 p.Ser155fs (c.463dup) is classified Pathogenic/Likely pathogenic in LAMB3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-21). Very rare (popmax 0.00517%, nfe); Associated with amelogenesis imperfecta type 1A.

What condition is associated with LAMB3 p.Ser155fs (c.463dup)?

LAMB3 p.Ser155fs (c.463dup) is associated with amelogenesis imperfecta type 1A, junctional epidermolysis bullosa, non-Herlitz type, junctional epidermolysis bullosa Herlitz type (ClinVar).

How common is LAMB3 p.Ser155fs (c.463dup) in the general population?

LAMB3 p.Ser155fs (c.463dup) is very rare (popmax 0.00517%, nfe) (gnomAD).

LAMB3 p.Ser155fs

c.463dup · rs776537364 · VCV188937

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Conditions

amelogenesis imperfecta type 1A

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 5.3	GERP -0.32, phastCons 0.98
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00517% European (non-Finnish) · 61/1,180,036 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00384% 62/1,614,024 alleles · very rare exomes 59/1,461,888 · genomes 3/152,136 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,345
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Ser155fs
Coding: c.463dup
MANE Select: NM_000228
dbSNP: rs776537364
Type: Duplication
Location: chr1:209634547 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 155: the laminin n-terminal domain

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

Disease context

amelogenesis imperfecta type 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: junctional epidermolysis bullosa, non-Herlitz type junctional epidermolysis bullosa Herlitz type

Similar variants

LAMB3 p.Asn345fs Pathogenic ★★ same condition
LAMB3 p.Cys546fs Pathogenic ★★ same condition
LAMB3 p.Leu11fs Pathogenic/Likely pathogenic ★★ same condition
LAMB3 c.2702-12dup Benign ★★ same condition
LAMB3 c.28+2dup Likely pathogenic ★ same condition
LAMB3 p.Ser608fs Pathogenic ★ same condition
LAMB3 p.Glu1132fs Pathogenic same condition
LAMB3 p.Ser800fs 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-ser155fs (accessed [today's date]).

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