Is LAMC3 p.Pro174= (c.522C>G) pathogenic?

LAMC3 p.Pro174= (c.522C>G) is classified Benign in LAMC3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-11-27). Common (popmax 28.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with occipital pachygyria and polymicrogyria.

What condition is associated with LAMC3 p.Pro174= (c.522C>G)?

LAMC3 p.Pro174= (c.522C>G) is associated with occipital pachygyria and polymicrogyria (ClinVar).

LAMC3 p.Pro174=

Q: How common is LAMC3 p.Pro174= (c.522C>G) in the general population?

LAMC3 p.Pro174= (c.522C>G) is common (popmax 28.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.522C>G · rs2275136 · VCV129471

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 28.6%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP 1.1
Overall
CADD	8.201	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.6% African / African-American · 21,421/74,978 alleles

Filtering AF 28.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.1%

Overall 13.3% 214,032/1,613,492 alleles · common exomes 189,268/1,461,274 · genomes 24,764/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	28.6%	4
Middle Eastern	24.4%	4
Ashkenazi Jewishnot grpmax-eligible	19%	5
Remaining individualsnot grpmax-eligible	14.5%	7
European (non-Finnish)	13.2%	8
Amishnot grpmax-eligible	11.7%	9
Admixed American	10.4%	10
East Asian	7.82%	13
South Asian	7.48%	13
Finnishnot grpmax-eligible	6.2%	16

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.Pro174=
Coding: c.522C>G
MANE Select: NM_006059
dbSNP: rs2275136
Type: single nucleotide variant
Location: chr9:131026433 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 174: 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.Pro174His Benign ★★ 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-pro174 (accessed [today's date]).

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