Is LAMB3 p.Asp309= (c.927C>T) pathogenic?

LAMB3 p.Asp309= (c.927C>T) is classified Conflicting classifications of pathogenicity in LAMB3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-12). Rare (popmax 0.132%, mid); Associated with junctional epidermolysis bullosa.

What condition is associated with LAMB3 p.Asp309= (c.927C>T)?

LAMB3 p.Asp309= (c.927C>T) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMB3 p.Asp309= (c.927C>T) in the general population?

LAMB3 p.Asp309= (c.927C>T) is rare (popmax 0.132%, mid) (gnomAD).

LAMB3 p.Asp309=

c.927C>T · rs141059189 · VCV295123

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

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 -0.24	GERP -3.9, phastCons 0.002
Overall
CADD	5.881	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Middle Eastern · 8/6,062 alleles

Filtering AF 0.0656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.0166% 268/1,614,148 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	758
European (non-Finnish)	0.0203%	4,937
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Admixed American	0.01%	10,003
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Finnishnot grpmax-eligible	0.00312%	32,012
African / African-American	0.00266%	37,524
East Asian	0.00223%	44,884
South Asian	0.0022%	45,539

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.Asp309=
Coding: c.927C>T
MANE Select: NM_000228
dbSNP: rs141059189
Type: single nucleotide variant
Location: chr1:209630631 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 309: the laminin egf-like 1 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 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
LAMB3 p.Arg635Ter 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-asp309 (accessed [today's date]).

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