Is LAMC3 p.Val112fs (c.332dup) pathogenic?

LAMC3 p.Val112fs (c.332dup) is classified Pathogenic in LAMC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-13). Absent from gnomAD; Associated with occipital pachygyria and polymicrogyria.

What condition is associated with LAMC3 p.Val112fs (c.332dup)?

LAMC3 p.Val112fs (c.332dup) is associated with occipital pachygyria and polymicrogyria (ClinVar).

How common is LAMC3 p.Val112fs (c.332dup) in the general population?

LAMC3 p.Val112fs (c.332dup) is absent from gnomAD (gnomAD).

LAMC3 p.Val112fs

c.332dup · rs2133193948 · VCV1376853

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

occipital pachygyria and polymicrogyria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.81	GERP -1.6, phastCons 0.006

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LAMC3
Protein: p.Val112fs
Coding: c.332dup
MANE Select: NM_006059
dbSNP: rs2133193948
Type: Duplication
Location: chr9:131009544 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 112: the laminin n-terminal domain

Full LAMC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

occipital pachygyria and polymicrogyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMC3 p.Pro1142fs Pathogenic ★ same condition
LAMC3 p.Pro15_Ala17dup Conflicting classifications of pathogenicity ★ same condition
LAMC3 p.Val112Met Uncertain significance ★ ⚠ same residue
LAMC3 p.Val112= Likely benign ★ same residue
LAMC3 c.1166-1G>A Likely pathogenic ★★ same condition
LAMC3 c.3211+2T>C Likely pathogenic ★★ same condition
LAMC3 c.809+2_809+8del Likely pathogenic ★★ same condition
LAMC3 p.Asp1168fs Pathogenic/Likely 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/lamc3-p-val112fs (accessed [today's date]).

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