Is LAMC3 p.Arg186= (c.558C>T) pathogenic?

LAMC3 p.Arg186= (c.558C>T) is classified Benign/Likely benign in LAMC3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-01). Low-frequency (popmax 1.32%, eas); Associated with occipital pachygyria and polymicrogyria.

What condition is associated with LAMC3 p.Arg186= (c.558C>T)?

LAMC3 p.Arg186= (c.558C>T) is associated with occipital pachygyria and polymicrogyria (ClinVar).

How common is LAMC3 p.Arg186= (c.558C>T) in the general population?

LAMC3 p.Arg186= (c.558C>T) is low-frequency (popmax 1.32%, eas) (gnomAD).

LAMC3 p.Arg186=

c.558C>T · rs2275135 · VCV378065

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.32%, eas)

Conditions

occipital pachygyria and polymicrogyria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7	GERP -4.3
Overall
CADD	5.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.32% East Asian · 594/44,880 alleles

Filtering AF 1.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2%

Overall 0.208% 3,355/1,613,358 alleles · low-frequency exomes 3,173/1,460,984 · genomes 182/152,374 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.32%	76
Amishnot grpmax-eligible	0.658%	152
South Asian	0.241%	416
European (non-Finnish)	0.196%	511
Remaining individualsnot grpmax-eligible	0.16%	625
Finnishnot grpmax-eligible	0.148%	676
Middle Eastern	0.066%	1,516
Admixed American	0.0283%	3,528
African / African-American	0.016%	6,254

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.Arg186=
Coding: c.558C>T
MANE Select: NM_006059
dbSNP: rs2275135
Type: single nucleotide variant
Location: chr9:131026469 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 186: 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.Arg186His 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
LAMC3 p.Arg1205Trp 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-arg186 (accessed [today's date]).

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