Is LAMC3 p.Pro622Arg (c.1865C>G) pathogenic?

LAMC3 p.Pro622Arg (c.1865C>G) is classified Conflicting classifications of pathogenicity in LAMC3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-07-01). AlphaMissense: likely benign (0.1379); Rare (popmax 0.296%, mid); Associated with Inborn genetic diseases.

What condition is associated with LAMC3 p.Pro622Arg (c.1865C>G)?

LAMC3 p.Pro622Arg (c.1865C>G) is associated with Inborn genetic diseases (ClinVar).

How common is LAMC3 p.Pro622Arg (c.1865C>G) in the general population?

LAMC3 p.Pro622Arg (c.1865C>G) is rare (popmax 0.296%, mid) (gnomAD).

What do computational predictors say about LAMC3 p.Pro622Arg (c.1865C>G)?

AlphaMissense predicts likely benign (score 0.1379) — an in-silico prediction, not a clinical call.

LAMC3 p.Pro622Arg

c.1865C>G · rs142041428 · VCV435736

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1379 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.296%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1379	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -4.46	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 3.8	GERP 1.9, phastCons 0.95
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.0039 · regional, not allelic
Overall
CADD	21.6	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 0.296% Middle Eastern · 18/6,084 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.158%

Overall 0.00855% 138/1,613,912 alleles · rare exomes 130/1,461,704 · genomes 8/152,208 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.296%	338
Admixed American	0.0283%	3,530
Remaining individualsnot grpmax-eligible	0.0208%	4,806
South Asian	0.00988%	10,121
African / African-American	0.00801%	12,488
European (non-Finnish)	0.00636%	15,733

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.Pro622Arg
Coding: c.1865C>G
MANE Select: NM_006059
dbSNP: rs142041428
Type: single nucleotide variant
Location: chr9:131052891 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 622: 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.Pro622His Uncertain significance ★★ ⚠ same residue
LAMC3 p.Pro622= Likely benign ★★ same residue
LAMC3 p.Pro622Leu Uncertain significance ★ ⚠ same residue
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

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-pro622arg (accessed [today's date]).

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