Is LAMC2 p.Arg1153= (c.3459G>A) pathogenic?

LAMC2 p.Arg1153= (c.3459G>A) is classified Conflicting classifications of pathogenicity in LAMC2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-20). Rare (popmax 0.238%, nfe); Associated with junctional epidermolysis bullosa.

What condition is associated with LAMC2 p.Arg1153= (c.3459G>A)?

LAMC2 p.Arg1153= (c.3459G>A) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMC2 p.Arg1153= (c.3459G>A) in the general population?

LAMC2 p.Arg1153= (c.3459G>A) is rare (popmax 0.238%, nfe) (gnomAD).

LAMC2 p.Arg1153=

c.3459G>A · rs140649374 · VCV294022

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.238%, nfe)

Conditions

junctional epidermolysis bullosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -3.8, phastCons 0.49
Overall
CADD	6.391	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.238% European (non-Finnish) · 2,812/1,180,034 alleles

Filtering AF 0.231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.228%

Overall 0.19% 3,070/1,614,178 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.238%	420
Remaining individualsnot grpmax-eligible	0.181%	553
Admixed American	0.08%	1,250
Middle Eastern	0.066%	1,516
Finnishnot grpmax-eligible	0.0547%	1,830
African / African-American	0.0506%	1,975
South Asian	0.0198%	5,060
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asian	0.00223%	44,880

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.Arg1153=
Coding: c.3459G>A
MANE Select: NM_005562
dbSNP: rs140649374
Type: single nucleotide variant
Location: chr1:183243277 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 1153: the 'domain ii and i' region

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-arg1153 (accessed [today's date]).

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