Is LAMC2 p.Ala796Val (c.2387C>T) pathogenic?

LAMC2 p.Ala796Val (c.2387C>T) is classified Conflicting classifications of pathogenicity in LAMC2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0957); Rare (popmax 0.187%, amr); Associated with junctional epidermolysis bullosa.

What condition is associated with LAMC2 p.Ala796Val (c.2387C>T)?

LAMC2 p.Ala796Val (c.2387C>T) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMC2 p.Ala796Val (c.2387C>T) in the general population?

LAMC2 p.Ala796Val (c.2387C>T) is rare (popmax 0.187%, amr) (gnomAD).

What do computational predictors say about LAMC2 p.Ala796Val (c.2387C>T)?

AlphaMissense predicts likely benign (score 0.0957) — an in-silico prediction, not a clinical call.

LAMC2 p.Ala796Val

c.2387C>T · rs139718245 · VCV294008

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0957 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.187%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

junctional epidermolysis bullosa

Computational evidence

Protein change
AlphaMissense	0.0957	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -6.49	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 1.1	GERP 1.1, phastCons 0.54
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.91 · regional, not allelic
Overall
CADD	15.55	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 0.187% Admixed American · 112/60,036 alleles

Filtering AF 0.158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.148%

Overall 0.118% 1,908/1,614,230 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.187%	536
European (non-Finnish)	0.143%	700
Remaining individualsnot grpmax-eligible	0.106%	947
African / African-American	0.0293%	3,411
Finnishnot grpmax-eligible	0.0219%	4,575
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
South Asian	0.00549%	18,218
East Asian	0.00446%	22,444

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.Ala796Val
Coding: c.2387C>T
MANE Select: NM_005562
dbSNP: rs139718245
Type: single nucleotide variant
Location: chr1:183235661 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 796: 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.Ala796= 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-ala796val (accessed [today's date]).

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