Is LAMC2 p.Phe51fs (c.146_150dup) pathogenic?

LAMC2 p.Phe51fs (c.146150dup) is classified Pathogenic/Likely pathogenic in LAMC2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-02-05). Very rare (popmax 0.000254%, nfe); Associated with LAMC2-related disorder.

What condition is associated with LAMC2 p.Phe51fs (c.146_150dup)?

LAMC2 p.Phe51fs (c.146_150dup) is associated with LAMC2-related disorder, junctional epidermolysis bullosa Herlitz type, epidermolysis bullosa, junctional 3A, intermediate (ClinVar).

How common is LAMC2 p.Phe51fs (c.146_150dup) in the general population?

LAMC2 p.Phe51fs (c.146_150dup) is very rare (popmax 0.000254%, nfe) (gnomAD).

LAMC2 p.Phe51fs

c.146_150dup · rs1057517353 · VCV371541

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

LAMC2-related disorder

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 2 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.094	GERP -4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,852 alleles

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

Overall 0.000205% 3/1,461,838 alleles · very rare

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: LAMC2
Protein: p.Phe51fs
Coding: c.146_150dup
MANE Select: NM_005562
dbSNP: rs1057517353
Type: Duplication
Location: chr1:183207945 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 51: the laminin egf-like 1 domain; a disulfide bond

Full LAMC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

LAMC2-related disorder

Also linked: junctional epidermolysis bullosa Herlitz type epidermolysis bullosa, junctional 3A, intermediate epidermolysis bullosa, junctional 3B, severe

Similar variants

LAMC2 p.Ala878fs Likely pathogenic ★ same condition
LAMC2 p.Asn739fs Likely pathogenic ★ same condition
LAMC2 p.Asn901fs Likely pathogenic ★ same condition
LAMC2 p.Asp568fs Likely pathogenic ★ same condition
LAMC2 p.Gln788fs Likely pathogenic ★ same condition
LAMC2 p.Phe51= Likely benign ★ same residue
LAMC2 p.Asp61Ter Likely pathogenic same condition
LAMC2 p.Gly448fs 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/lamc2-p-phe51fs (accessed [today's date]).

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