Is LAMC2 p.Arg170Pro (c.509G>C) pathogenic?

LAMC2 p.Arg170Pro (c.509G>C) is classified Uncertain significance in LAMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely benign (0.3249); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with LAMC2 p.Arg170Pro (c.509G>C)?

LAMC2 p.Arg170Pro (c.509G>C) is associated with Inborn genetic diseases (ClinVar).

How common is LAMC2 p.Arg170Pro (c.509G>C) in the general population?

LAMC2 p.Arg170Pro (c.509G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about LAMC2 p.Arg170Pro (c.509G>C)?

AlphaMissense predicts likely benign (score 0.3249) — an in-silico prediction, not a clinical call.

LAMC2 p.Arg170Pro

c.509G>C · VCV4623521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3249 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3249	likely benign
REVEL	0.331	indeterminate
SaProt	LLR -9.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -2.1, phastCons 0.004
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.031 · regional, not allelic
Overall
CADD	19.35	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Overall 0.000657% 1/152,258 alleles · very rare

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: LAMC2
Protein: p.Arg170Pro
Coding: c.509G>C
MANE Select: NM_005562
Type: single nucleotide variant
Location: chr1:183220830 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 170: a disulfide bond; the laminin egf-like 3 domain

Full LAMC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMC2 p.Arg170Gln Uncertain significance ★ ⚠ same residue
LAMC2 p.Arg170Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
LAMC2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same residue
LAMC2 p.Asp247His Uncertain significance ★★ ⚠ same condition
LAMC2 p.Gln1005Arg Uncertain significance ★★ ⚠ same condition
LAMC2 p.Glu1160Asp Uncertain significance ★★ ⚠ same condition
LAMC2 p.Gly278Arg Uncertain significance ★★ ⚠ same condition
LAMC2 p.Gly672Ala 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/lamc2-p-arg170pro (accessed [today's date]).

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