Is LAMC2 p.Ala878= (c.2634G>A) pathogenic?

LAMC2 p.Ala878= (c.2634G>A) is classified Conflicting classifications of pathogenicity in LAMC2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-25). Rare (popmax 0.227%, afr); Associated with junctional epidermolysis bullosa.

What condition is associated with LAMC2 p.Ala878= (c.2634G>A)?

LAMC2 p.Ala878= (c.2634G>A) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMC2 p.Ala878= (c.2634G>A) in the general population?

LAMC2 p.Ala878= (c.2634G>A) is rare (popmax 0.227%, afr) (gnomAD).

LAMC2 p.Ala878=

c.2634G>A · rs148925665 · VCV294010

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.227%, afr)

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 -3.3	GERP 0.92
Overall
CADD	7.045	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.227% African / African-American · 170/75,028 alleles

Filtering AF 0.199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.188%

Overall 0.0269% 435/1,614,110 alleles · rare exomes 324/1,461,848 · genomes 111/152,262 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.227%	441
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0544%	1,838
South Asian	0.0198%	5,059
Admixed American	0.0183%	5,457
European (non-Finnish)	0.0162%	6,178
East Asian	0.00891%	11,221
Finnishnot grpmax-eligible	0.00312%	32,015

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.Ala878=
Coding: c.2634G>A
MANE Select: NM_005562
dbSNP: rs148925665
Type: single nucleotide variant
Location: chr1:183237384 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 878: 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.Ala878Val Uncertain significance ★ ⚠ same residue
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

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-ala878 (accessed [today's date]).

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