Is LAMC3 p.Arg606Ser (c.1818G>C) pathogenic?

LAMC3 p.Arg606Ser (c.1818G>C) is classified Uncertain significance in LAMC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-25). AlphaMissense: likely benign (0.1117); Ultra-rare (popmax 0.0653%, afr); Associated with Inborn genetic diseases.

What condition is associated with LAMC3 p.Arg606Ser (c.1818G>C)?

LAMC3 p.Arg606Ser (c.1818G>C) is associated with Inborn genetic diseases (ClinVar).

How common is LAMC3 p.Arg606Ser (c.1818G>C) in the general population?

LAMC3 p.Arg606Ser (c.1818G>C) is ultra-rare (popmax 0.0653%, afr) (gnomAD).

What do computational predictors say about LAMC3 p.Arg606Ser (c.1818G>C)?

AlphaMissense predicts likely benign (score 0.1117) — an in-silico prediction, not a clinical call.

LAMC3 p.Arg606Ser

c.1818G>C · rs138907739 · VCV1435611

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1117 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0653%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1117	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -8.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.94	GERP -3.5
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.0039 · regional, not allelic
Overall
CADD	0.215	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 0.0653% African / African-American · 49/75,034 alleles

Filtering AF 0.0507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0455%

Overall 0.00316% 51/1,613,270 alleles · ultra-rare exomes 18/1,460,976 · genomes 33/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0653%	1,531
Middle Eastern	0.0167%	5,984
Admixed American	0.00167%	59,988

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.Arg606Ser
Coding: c.1818G>C
MANE Select: NM_006059
dbSNP: rs138907739
Type: single nucleotide variant
Location: chr9:131052678 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 606: the laminin iv type a domain

Full LAMC3 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

LAMC3 p.Gln550Ter Pathogenic ★★ same condition
LAMC3 p.Ser421Ter Pathogenic ★★ same condition
LAMC3 p.Ala109Pro Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1137Pro Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1137Thr Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1161Val Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1183Thr Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1244Thr 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-arg606ser (accessed [today's date]).

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