Is LAMC2 p.Arg533Trp (c.1597C>T) pathogenic?

LAMC2 p.Arg533Trp (c.1597C>T) is classified Uncertain significance in LAMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-16). AlphaMissense: likely benign (0.0926); Very rare (popmax 0.00167%, amr); Associated with junctional epidermolysis bullosa.

What condition is associated with LAMC2 p.Arg533Trp (c.1597C>T)?

LAMC2 p.Arg533Trp (c.1597C>T) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMC2 p.Arg533Trp (c.1597C>T) in the general population?

LAMC2 p.Arg533Trp (c.1597C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about LAMC2 p.Arg533Trp (c.1597C>T)?

AlphaMissense predicts likely benign (score 0.0926) — an in-silico prediction, not a clinical call.

LAMC2 p.Arg533Trp

c.1597C>T · rs1029109781 · VCV876090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0926 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

junctional epidermolysis bullosa

Computational evidence

Protein change
AlphaMissense	0.0926	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -13.17	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.097, phastCons 0.88
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.031 · regional, not allelic
Overall
CADD	26.6	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 0.00167% Admixed American · 1/59,972 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00124% 20/1,613,710 alleles · very rare exomes 14/1,461,890 · genomes 6/151,820 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,972
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.00144%	69,411
South Asian	0.0011%	91,016

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.Arg533Trp
Coding: c.1597C>T
MANE Select: NM_005562
dbSNP: rs1029109781
Type: single nucleotide variant
Location: chr1:183228502 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 533: the laminin egf-like 7 domain

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

Disease context

junctional epidermolysis bullosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMC2 p.Arg533Gln Uncertain significance ★ ⚠ same residue
LAMC2 p.Arg533Pro Uncertain significance ★ ⚠ same residue
LAMC2 p.Arg533= Likely benign ★ same residue
LAMC2 p.Arg1129Ter Pathogenic ★★ same condition
LAMC2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 p.Arg349Ter Pathogenic ★★ same condition
LAMC2 p.Gln692Ter Pathogenic/Likely pathogenic ★★ 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-arg533trp (accessed [today's date]).

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