Is LAMB3 p.Ser1068= (c.3204C>T) pathogenic?

LAMB3 p.Ser1068= (c.3204C>T) is classified Conflicting classifications of pathogenicity in LAMB3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-01-20). Ultra-rare (popmax 0.0195%, mid); Associated with junctional epidermolysis bullosa.

What condition is associated with LAMB3 p.Ser1068= (c.3204C>T)?

LAMB3 p.Ser1068= (c.3204C>T) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMB3 p.Ser1068= (c.3204C>T) in the general population?

LAMB3 p.Ser1068= (c.3204C>T) is ultra-rare (popmax 0.0195%, mid) (gnomAD).

LAMB3 p.Ser1068=

c.3204C>T · rs768257008 · VCV295067

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 0.0195%, mid)

Conditions

junctional epidermolysis bullosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Constraint at this position
Conservation	phyloP -0.34	GERP -3
Overall
CADD	10.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0195% Middle Eastern · 1/5,134 alleles

Filtering AF 0.00677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00626% 101/1,612,682 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0195%	5,134
South Asian	0.0121%	8,275
European (non-Finnish)	0.00669%	14,937
Remaining individualsnot grpmax-eligible	0.00641%	15,592
East Asian	0.00445%	22,448
Admixed American	0.00333%	30,005
African / African-American	0.00267%	37,434

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.Ser1068=
Coding: c.3204C>T
MANE Select: NM_000228
dbSNP: rs768257008
Type: single nucleotide variant
Location: chr1:209617434 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 1068: the 'domain i' region

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-ser1068 (accessed [today's date]).

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