Is LAMC2 p.Val161= (c.483C>T) pathogenic?

LAMC2 p.Val161= (c.483C>T) is classified Benign in LAMC2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 39.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with junctional epidermolysis bullosa.

What condition is associated with LAMC2 p.Val161= (c.483C>T)?

LAMC2 p.Val161= (c.483C>T) is associated with junctional epidermolysis bullosa, junctional epidermolysis bullosa, non-Herlitz type, junctional epidermolysis bullosa Herlitz type (ClinVar).

LAMC2 p.Val161=

Q: How common is LAMC2 p.Val161= (c.483C>T) in the general population?

LAMC2 p.Val161= (c.483C>T) is common (popmax 39.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.483C>T · rs1129723 · VCV259789

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 39.1%, afr) — too common for a highly-penetrant pathogenic allele

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 2.2	GERP 1.6, phastCons 1
Overall
CADD	12.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 39.1% African / African-American · 29,293/74,900 alleles

Filtering AF 38.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 38.6%

Overall 21.4% 344,684/1,612,612 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	39.1%	3
East Asian	39%	3
Admixed American	35%	3
South Asian	31.1%	3
Remaining individualsnot grpmax-eligible	22.2%	5
Finnishnot grpmax-eligible	18.5%	5
European (non-Finnish)	18.4%	5
Ashkenazi Jewishnot grpmax-eligible	16.7%	6
Middle Eastern	12.8%	8
Amishnot grpmax-eligible	10.1%	10

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.Val161=
Coding: c.483C>T
MANE Select: NM_005562
dbSNP: rs1129723
Type: single nucleotide variant
Location: chr1:183218468 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 161: the laminin egf-like 3 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

Also linked: junctional epidermolysis bullosa, non-Herlitz type junctional epidermolysis bullosa Herlitz type

Similar variants

LAMC2 c.268+1G>A Likely pathogenic ★★ same condition
LAMC2 p.Arg1129Ter Pathogenic ★★ same condition
LAMC2 p.Arg115Ter Pathogenic ★★ same condition
LAMC2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 p.Arg223Ter Pathogenic ★★ same condition
LAMC2 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 p.Arg349Ter Pathogenic ★★ same condition
LAMC2 p.Arg95Ter 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-val161 (accessed [today's date]).

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