Is LAMC3 p.Arg173Pro (c.518G>C) pathogenic?

LAMC3 p.Arg173Pro (c.518G>C) is classified Uncertain significance in LAMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: ambiguous (0.423); Ultra-rare (popmax 0.0312%, eas); Associated with occipital pachygyria and polymicrogyria.

What condition is associated with LAMC3 p.Arg173Pro (c.518G>C)?

LAMC3 p.Arg173Pro (c.518G>C) is associated with occipital pachygyria and polymicrogyria (ClinVar).

How common is LAMC3 p.Arg173Pro (c.518G>C) in the general population?

LAMC3 p.Arg173Pro (c.518G>C) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about LAMC3 p.Arg173Pro (c.518G>C)?

AlphaMissense predicts ambiguous (score 0.423) — an in-silico prediction, not a clinical call.

LAMC3 p.Arg173Pro

c.518G>C · VCV3596487

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.423 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Conditions

occipital pachygyria and polymicrogyria

Computational evidence

Protein change
AlphaMissense	0.423	ambiguous
REVEL	0.468	indeterminate
SaProt	LLR -12.69	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.31	GERP -0.23
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.0039 · regional, not allelic
Overall
CADD	19.34	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 0.0312% East Asian · 14/44,884 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.000929% 15/1,613,792 alleles · ultra-rare exomes 15/1,461,412 · genomes 0/152,380 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,206
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Arg173Pro
Coding: c.518G>C
MANE Select: NM_006059
Type: single nucleotide variant
Location: chr9:131026429 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 173: 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.Arg173Trp Benign/Likely benign ★★ same residue
LAMC3 p.Arg173Gln Uncertain significance ★ ⚠ same residue
LAMC3 c.1166-1G>A Likely pathogenic ★★ same condition
LAMC3 c.3211+2T>C Likely pathogenic ★★ same condition
LAMC3 p.Ala1090Thr Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1163Thr Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala79Val Uncertain significance ★★ ⚠ same condition
LAMC3 p.Arg1167Gly 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-arg173pro (accessed [today's date]).

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