Is LAMB3 p.Ser1144= (c.3432A>G) pathogenic?

LAMB3 p.Ser1144= (c.3432A>G) is classified Benign in LAMB3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 61.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with amelogenesis imperfecta type 1A.

What condition is associated with LAMB3 p.Ser1144= (c.3432A>G)?

LAMB3 p.Ser1144= (c.3432A>G) is associated with amelogenesis imperfecta type 1A, junctional epidermolysis bullosa, non-Herlitz type, junctional epidermolysis bullosa Herlitz type (ClinVar).

LAMB3 p.Ser1144=

Q: How common is LAMB3 p.Ser1144= (c.3432A>G) in the general population?

LAMB3 p.Ser1144= (c.3432A>G) is common (popmax 61.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3432A>G · rs1049607 · VCV255595

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 61.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

amelogenesis imperfecta type 1A

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 -20	GERP -3.4
Overall
CADD	0.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 61.4% African / African-American · 45,990/74,914 alleles

Filtering AF 60.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.7%

Overall 37.9% 610,710/1,612,508 alleles · common exomes 544,006/1,460,392 · genomes 66,704/152,116 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	61.4%	2
Ashkenazi Jewishnot grpmax-eligible	41.9%	2
East Asian	41.4%	2
South Asian	40.2%	2
Finnishnot grpmax-eligible	38.9%	3
Remaining individualsnot grpmax-eligible	38.3%	3
Admixed American	38%	3
European (non-Finnish)	35.9%	3
Middle Eastern	33.4%	3
Amishnot grpmax-eligible	28.4%	4

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.Ser1144=
Coding: c.3432A>G
MANE Select: NM_000228
dbSNP: rs1049607
Type: single nucleotide variant
Location: chr1:209615358 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 1144: the 'domain i' region

Full LAMB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

amelogenesis imperfecta type 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: junctional epidermolysis bullosa, non-Herlitz type junctional epidermolysis bullosa Herlitz type junctional epidermolysis bullosa

Similar variants

LAMB3 p.Ser1144Ter Pathogenic same residue
LAMB3 c.1132+5G>A Pathogenic/Likely pathogenic ★★ same condition
LAMB3 c.1133-22G>A Pathogenic ★★ same condition
LAMB3 c.1288+1G>T Pathogenic/Likely pathogenic ★★ same condition
LAMB3 c.1486-1G>A Likely pathogenic ★★ same condition
LAMB3 c.1597+1G>T Likely pathogenic ★★ same condition
LAMB3 c.2701+2T>C Likely pathogenic ★★ same condition
LAMB3 c.28+1G>T 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/lamb3-p-ser1144 (accessed [today's date]).

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