Is LAMC2 p.Asp136Val (c.407A>T) pathogenic?

LAMC2 p.Asp136Val (c.407A>T) is classified Benign in LAMC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1069); Low-frequency (popmax 4.56%, eas); Associated with junctional epidermolysis bullosa.

What condition is associated with LAMC2 p.Asp136Val (c.407A>T)?

LAMC2 p.Asp136Val (c.407A>T) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMC2 p.Asp136Val (c.407A>T) in the general population?

LAMC2 p.Asp136Val (c.407A>T) is low-frequency (popmax 4.56%, eas) (gnomAD).

What do computational predictors say about LAMC2 p.Asp136Val (c.407A>T)?

AlphaMissense predicts likely benign (score 0.1069) — an in-silico prediction, not a clinical call.

LAMC2 p.Asp136Val

c.407A>T · rs12037099 · VCV293991

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1069 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.56%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

junctional epidermolysis bullosa

Computational evidence

Protein change
AlphaMissense	0.1069	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP -0.63, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.031 · regional, not allelic
Overall
CADD	18.69	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.56% East Asian · 2,048/44,870 alleles

Filtering AF 4.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.33%

Overall 0.161% 2,603/1,613,320 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	4.56%	22
Remaining individualsnot grpmax-eligible	0.245%	408
South Asian	0.21%	477
Admixed American	0.195%	513
Middle Eastern	0.033%	3,029
African / African-American	0.0133%	7,492
European (non-Finnish)	0.00661%	15,121
Finnishnot grpmax-eligible	0.00625%	15,994

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.Asp136Val
Coding: c.407A>T
MANE Select: NM_005562
dbSNP: rs12037099
Type: single nucleotide variant
Location: chr1:183218392 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 136: a UniProt-annotated variant site (in)

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.Asp136= Likely benign ★ 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-asp136val (accessed [today's date]).

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