Is LAMC3 p.Pro779fs (c.2336del) pathogenic?

LAMC3 p.Pro779fs (c.2336del) is classified Pathogenic/Likely pathogenic in LAMC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-28). Very rare (popmax 0.000187%); Associated with LAMC3-related disorder.

What condition is associated with LAMC3 p.Pro779fs (c.2336del)?

LAMC3 p.Pro779fs (c.2336del) is associated with LAMC3-related disorder (ClinVar).

How common is LAMC3 p.Pro779fs (c.2336del) in the general population?

LAMC3 p.Pro779fs (c.2336del) is very rare (popmax 0.000187%) (gnomAD).

LAMC3 p.Pro779fs

c.2336del · rs765163533 · VCV1454553

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000187%)

Conditions

LAMC3-related disorder

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 13 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000187%

Overall 0.000187% 3/1,607,284 alleles · very rare exomes 3/1,454,986 · genomes 0/152,298 · joint denominator

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: LAMC3
Protein: p.Pro779fs
Coding: c.2336del
MANE Select: NM_006059
dbSNP: rs765163533
Type: Deletion
Location: chr9:131061207 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 779: the laminin egf-like 7 domain

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

Disease context

LAMC3-related disorder

Similar variants

LAMC3 p.Phe623fs Pathogenic ★ same condition
LAMC3 p.Thr232fs Likely pathogenic ★ same condition
LAMC3 p.Pro779Leu Uncertain significance ★ ⚠ same residue
LAMC3 p.Pro779= Likely benign ★ same residue
LAMC3 c.4231-12C>G Likely pathogenic ★ same condition
LAMC3 c.976+1G>C Conflicting classifications of pathogenicity ★ same condition
LAMC3 p.Gly795Trp Uncertain significance ★ ⚠ same condition
LAMC3 p.Gln1012= Likely benign 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-pro779fs (accessed [today's date]).

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