Is LAMC3 p.Pro700fs (c.2096dup) pathogenic?

LAMC3 p.Pro700fs (c.2096dup) is classified Pathogenic in LAMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). Very rare (popmax 8.47e-05%, nfe).

How common is LAMC3 p.Pro700fs (c.2096dup) in the general population?

LAMC3 p.Pro700fs (c.2096dup) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

LAMC3 p.Pro700fs

c.2096dup · rs1834422790 · VCV2846631

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 12 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.3	GERP -4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,020 alleles

Overall 0.000124% 2/1,614,164 alleles · very rare exomes 2/1,461,834 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)grpmax	8.47e-05%	1,180,020

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro700fs
Coding: c.2096dup
MANE Select: NM_006059
dbSNP: rs1834422790
Type: Duplication
Location: chr9:131057079 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 700: the laminin egf-like 5; second part domain

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

Similar variants

LAMC3 p.Pro700Leu Uncertain significance ★ ⚠ same residue
LAMC3 p.Val112fs Pathogenic ★★ same type
LAMC3 p.Ala1170_Ala1175dup Uncertain significance ★★ same type
LAMC3 p.Gln1011fs Pathogenic ★ same type
LAMC3 p.Gln524fs Pathogenic ★ same type
LAMC3 p.Gln781fs Pathogenic ★ same type
LAMC3 p.Gly567fs Pathogenic ★ same type
LAMC3 p.Gly795fs Pathogenic ★ same type

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-pro700fs (accessed [today's date]).

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