Is LAMB3 p.Ser512= (c.1536C>T) pathogenic?

LAMB3 p.Ser512= (c.1536C>T) is classified Conflicting classifications of pathogenicity in LAMB3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-04-19). Ultra-rare (popmax 0.0117%, amr); Associated with junctional epidermolysis bullosa.

What condition is associated with LAMB3 p.Ser512= (c.1536C>T)?

LAMB3 p.Ser512= (c.1536C>T) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMB3 p.Ser512= (c.1536C>T) in the general population?

LAMB3 p.Ser512= (c.1536C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

LAMB3 p.Ser512=

c.1536C>T · rs375260663 · VCV295107

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

junctional epidermolysis bullosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.6	GERP -3.9
Overall
CADD	0.745	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,002 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00143% 23/1,613,708 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,572
African / African-American	0.00133%	74,954
European (non-Finnish)	0.00127%	78,664

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: LAMB3
Protein: p.Ser512=
Coding: c.1536C>T
MANE Select: NM_000228
dbSNP: rs375260663
Type: single nucleotide variant
Location: chr1:209626928 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 512: the laminin egf-like 5 domain

Full LAMB3 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

LAMB3 p.Ser512Arg Uncertain significance ★ ⚠ same residue
LAMB3 c.1132+5G>A Pathogenic/Likely pathogenic ★★ same condition
LAMB3 c.1486-1G>A Likely pathogenic ★★ same condition
LAMB3 c.3228+1G>A Pathogenic ★★ same condition
LAMB3 c.565-2A>G Pathogenic ★★ same condition
LAMB3 c.628+1G>A Pathogenic/Likely pathogenic ★★ same condition
LAMB3 c.823-1G>A Pathogenic ★★ same condition
LAMB3 p.Arg144Ter 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/lamb3-p-ser512 (accessed [today's date]).

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