Is LAMC2 p.Ala497= (c.1491T>G) pathogenic?

LAMC2 p.Ala497= (c.1491T>G) is classified Benign/Likely benign in LAMC2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-19). Rare (popmax 0.504%, eas); Associated with junctional epidermolysis bullosa.

What condition is associated with LAMC2 p.Ala497= (c.1491T>G)?

LAMC2 p.Ala497= (c.1491T>G) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMC2 p.Ala497= (c.1491T>G) in the general population?

LAMC2 p.Ala497= (c.1491T>G) is rare (popmax 0.504%, eas) (gnomAD).

LAMC2 p.Ala497=

c.1491T>G · rs539212332 · VCV294004

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.504%, eas)

Conditions

junctional epidermolysis bullosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.4
Overall
CADD	0.054	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.504% East Asian · 226/44,864 alleles

Filtering AF 0.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.429%

Overall 0.0184% 297/1,614,164 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.504%	199
Remaining individualsnot grpmax-eligible	0.0352%	2,841
South Asian	0.0242%	4,140
Admixed American	0.00333%	30,014
European (non-Finnish)	0.00212%	47,201

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.Ala497=
Coding: c.1491T>G
MANE Select: NM_005562
dbSNP: rs539212332
Type: single nucleotide variant
Location: chr1:183228396 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 497: the laminin egf-like 6 domain

Full LAMC2 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

LAMC2 p.Arg1129Ter Pathogenic ★★ same condition
LAMC2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 p.Arg349Ter Pathogenic ★★ same condition
LAMC2 p.Gln692Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 p.Gln961Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 c.503+6T>C Uncertain significance ★★ same condition
LAMC2 c.*275A>C Uncertain significance ★★ 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-ala497 (accessed [today's date]).

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