Is LAMC2 p.Met1Val (c.1A>G) pathogenic?

LAMC2 p.Met1Val (c.1A>G) is classified Conflicting classifications of pathogenicity in LAMC2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-01-23). Very rare (popmax 0.00017%, nfe); Associated with epidermolysis bullosa, junctional 3A, intermediate.

What condition is associated with LAMC2 p.Met1Val (c.1A>G)?

LAMC2 p.Met1Val (c.1A>G) is associated with epidermolysis bullosa, junctional 3A, intermediate, junctional epidermolysis bullosa Herlitz type, junctional epidermolysis bullosa (ClinVar).

How common is LAMC2 p.Met1Val (c.1A>G) in the general population?

LAMC2 p.Met1Val (c.1A>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

LAMC2 p.Met1Val

c.1A>G · rs886045625 · VCV293984

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

epidermolysis bullosa, junctional 3A, intermediate

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.216	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.6, phastCons 1
Overall
CADD	22.5	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 0.00017% European (non-Finnish) · 2/1,178,204 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000138% 2/1,447,762 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.Met1Val
Coding: c.1A>G
MANE Select: NM_005562
dbSNP: rs886045625
Type: single nucleotide variant
Location: chr1:183186353 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89

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

Disease context

epidermolysis bullosa, junctional 3A, intermediate — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

LAMC2 p.Met1Ile Likely pathogenic same residue
LAMC2 p.Met1Thr Pathogenic ★ same residue
LAMC2 c.1715-2A>G Likely pathogenic ★★ same condition
LAMC2 c.268+1G>A Likely pathogenic ★★ same condition
LAMC2 c.3328+1G>A Pathogenic/Likely pathogenic ★★ same condition
LAMC2 c.640+1G>A Likely pathogenic ★★ same condition
LAMC2 p.Arg1129Ter Pathogenic ★★ same condition
LAMC2 p.Arg115Ter 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-met1val (accessed [today's date]).

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