Is LAMC3 p.Ser644= (c.1932C>T) pathogenic?

LAMC3 p.Ser644= (c.1932C>T) is classified Benign in LAMC3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 58.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with occipital pachygyria and polymicrogyria.

What condition is associated with LAMC3 p.Ser644= (c.1932C>T)?

LAMC3 p.Ser644= (c.1932C>T) is associated with occipital pachygyria and polymicrogyria (ClinVar).

LAMC3 p.Ser644=

Q: How common is LAMC3 p.Ser644= (c.1932C>T) in the general population?

LAMC3 p.Ser644= (c.1932C>T) is common (popmax 58.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1932C>T · rs12349966 · VCV129454

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 58.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

occipital pachygyria and polymicrogyria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.41	GERP -1.6, phastCons 0.005
Overall
CADD	5.924	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 58.2% African / African-American · 43,573/74,878 alleles

Filtering AF 57.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 57.5%

Overall 44.3% 712,333/1,608,202 alleles · common exomes 640,301/1,456,100 · genomes 72,032/152,102 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	58.2%	2
Finnishnot grpmax-eligible	47.6%	2
South Asian	45.2%	2
Middle Eastern	45%	2
European (non-Finnish)	44.2%	2
Remaining individualsnot grpmax-eligible	43.9%	2
East Asian	42.1%	2
Ashkenazi Jewishnot grpmax-eligible	34.9%	3
Amishnot grpmax-eligible	31.1%	3
Admixed American	30.2%	3

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.Ser644=
Coding: c.1932C>T
MANE Select: NM_006059
dbSNP: rs12349966
Type: single nucleotide variant
Location: chr9:131052958 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 644: 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 p.Ser644Ile Uncertain significance ★ ⚠ same residue
LAMC3 p.Ser644Gly 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-ser644 (accessed [today's date]).

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