Is LAMB3 p.Asp445= (c.1335C>T) pathogenic?

LAMB3 p.Asp445= (c.1335C>T) is classified Likely benign in LAMB3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-01). Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with LAMB3 p.Asp445= (c.1335C>T)?

LAMB3 p.Asp445= (c.1335C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LAMB3 p.Asp445= (c.1335C>T) in the general population?

LAMB3 p.Asp445= (c.1335C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

LAMB3 p.Asp445=

c.1335C>T · rs374430633 · VCV754996

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Inborn genetic diseases

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 -3.5	GERP -4.2
Overall
CADD	1.112	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00291% 47/1,614,048 alleles · ultra-rare exomes 36/1,461,760 · genomes 11/152,288 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.0134%	7,478
African / African-American	0.00933%	10,721
Admixed American	0.005%	20,009
South Asian	0.00329%	30,361
European (non-Finnish)	0.0022%	45,385
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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.Asp445=
Coding: c.1335C>T
MANE Select: NM_000228
dbSNP: rs374430633
Type: single nucleotide variant
Location: chr1:209627533 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 445: the laminin egf-like 4 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMB3 p.Ala1071Thr Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala1145Val Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala330Thr Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala330Val Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala590Val Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala825Thr Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala832Val Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala855Gly Uncertain significance ★★ ⚠ 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-asp445 (accessed [today's date]).

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