Is LAMC3 p.Leu7Pro (c.20T>C) pathogenic?

LAMC3 p.Leu7Pro (c.20T>C) is classified Uncertain significance in LAMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.1505); No allele count reported in gnomAD v4.1 (AN 1,250,698); Associated with Inborn genetic diseases.

What condition is associated with LAMC3 p.Leu7Pro (c.20T>C)?

LAMC3 p.Leu7Pro (c.20T>C) is associated with Inborn genetic diseases (ClinVar).

How common is LAMC3 p.Leu7Pro (c.20T>C) in the general population?

LAMC3 p.Leu7Pro (c.20T>C) is no allele count reported in gnomAD v4.1 (AN 1,250,698) (gnomAD).

What do computational predictors say about LAMC3 p.Leu7Pro (c.20T>C)?

AlphaMissense predicts likely benign (score 0.1505) — an in-silico prediction, not a clinical call.

LAMC3 p.Leu7Pro

c.20T>C · VCV4623546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1505 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,250,698)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1505	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -11.45	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.09	GERP -0.86, phastCons 0.002
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.0039 · regional, not allelic
Overall
CADD	16.59	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

No allele count reported in gnomAD v4.1 (AN 1,250,698). 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.Leu7Pro
Coding: c.20T>C
MANE Select: NM_006059
Type: single nucleotide variant
Location: chr9:131009234 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMC3 p.Leu7= Likely benign ★ same residue
LAMC3 p.Gln550Ter Pathogenic ★★ same condition
LAMC3 p.Ser421Ter Pathogenic ★★ same condition
LAMC3 p.Ala109Pro Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1137Pro Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1137Thr Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1161Val Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1183Thr 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/lamc3-p-leu7pro (accessed [today's date]).

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