Is LAMC3 p.Ala508= (c.1524C>T) pathogenic?

LAMC3 p.Ala508= (c.1524C>T) is classified Likely benign in LAMC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-14). Very rare (popmax 0.00392%, amr); Associated with occipital pachygyria and polymicrogyria.

What condition is associated with LAMC3 p.Ala508= (c.1524C>T)?

LAMC3 p.Ala508= (c.1524C>T) is associated with occipital pachygyria and polymicrogyria (ClinVar).

How common is LAMC3 p.Ala508= (c.1524C>T) in the general population?

LAMC3 p.Ala508= (c.1524C>T) is very rare (popmax 0.00392%, amr) (gnomAD).

LAMC3 p.Ala508=

c.1524C>T · rs753711099 · VCV1668575

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00392%, amr)

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 -12	GERP -3.8
Overall
CADD	4.262	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00392% Admixed American · 2/51,010 alleles

Filtering AF 0.00065% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000489%

Overall 0.00129% 20/1,547,696 alleles · very rare exomes 19/1,395,542 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00392%	25,505
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,620
East Asian	0.00245%	40,876
South Asian	0.00238%	41,983
Remaining individualsnot grpmax-eligible	0.00167%	59,922
European (non-Finnish)	0.00114%	87,996

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.Ala508=
Coding: c.1524C>T
MANE Select: NM_006059
dbSNP: rs753711099
Type: single nucleotide variant
Location: chr9:131049024 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 508: the laminin iv type a 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 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
LAMC3 p.Arg1351Trp 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-ala508 (accessed [today's date]).

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