Is LAMC3 p.His830Arg (c.2489A>G) pathogenic?

LAMC3 p.His830Arg (c.2489A>G) is classified Likely benign in LAMC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.0574); Rare (popmax 0.371%, afr); Associated with Inborn genetic diseases.

What condition is associated with LAMC3 p.His830Arg (c.2489A>G)?

LAMC3 p.His830Arg (c.2489A>G) is associated with Inborn genetic diseases (ClinVar).

How common is LAMC3 p.His830Arg (c.2489A>G) in the general population?

LAMC3 p.His830Arg (c.2489A>G) is rare (popmax 0.371%, afr) (gnomAD).

What do computational predictors say about LAMC3 p.His830Arg (c.2489A>G)?

AlphaMissense predicts likely benign (score 0.0574) — an in-silico prediction, not a clinical call.

LAMC3 p.His830Arg

c.2489A>G · rs145574848 · VCV1594504

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0574 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.371%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0574	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR 0.21	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 -4.1	GERP -4.3
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.0039 · regional, not allelic
Overall
CADD	0.027	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.371% African / African-American · 278/75,024 alleles

Filtering AF 0.335% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.321%

Overall 0.0193% 311/1,614,108 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.371%	270
Admixed American	0.0283%	3,531
Remaining individualsnot grpmax-eligible	0.0224%	4,465
South Asian	0.0011%	91,088
European (non-Finnish)	8.47e-05%	1,180,008

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.His830Arg
Coding: c.2489A>G
MANE Select: NM_006059
dbSNP: rs145574848
Type: single nucleotide variant
Location: chr9:131067101 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 830: the laminin egf-like 8 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-his830arg (accessed [today's date]).

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