Is LAMC2 p.Ala111Pro (c.331G>C) pathogenic?

LAMC2 p.Ala111Pro (c.331G>C) is classified Benign in LAMC2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0812); Common (popmax 11.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with junctional epidermolysis bullosa.

What condition is associated with LAMC2 p.Ala111Pro (c.331G>C)?

LAMC2 p.Ala111Pro (c.331G>C) is associated with junctional epidermolysis bullosa (ClinVar).

What do computational predictors say about LAMC2 p.Ala111Pro (c.331G>C)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

LAMC2 p.Ala111Pro

Q: How common is LAMC2 p.Ala111Pro (c.331G>C) in the general population?

LAMC2 p.Ala111Pro (c.331G>C) is common (popmax 11.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.331G>C · rs12065473 · VCV293988

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11.4%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

junctional epidermolysis bullosa

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -5.75	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 2.6	GERP -0.81, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.031 · regional, not allelic
Overall
CADD	15.05	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 11.4% African / African-American · 8,561/74,982 alleles

Filtering AF 11.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.1%

Overall 0.621% 10,023/1,614,132 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.4%	9
Remaining individualsnot grpmax-eligible	0.835%	120
Admixed American	0.795%	126
Middle Eastern	0.594%	168
European (non-Finnish)	0.0344%	2,907
South Asian	0.0231%	4,337

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.Ala111Pro
Coding: c.331G>C
MANE Select: NM_005562
dbSNP: rs12065473
Type: single nucleotide variant
Location: chr1:183215515 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 111: the laminin egf-like 2 domain; 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.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-ala111pro (accessed [today's date]).

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