Is LAMB3 p.Glu1069Gln (c.3205G>C) pathogenic?

LAMB3 p.Glu1069Gln (c.3205G>C) is classified Likely benign in LAMB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.0555); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with LAMB3 p.Glu1069Gln (c.3205G>C)?

LAMB3 p.Glu1069Gln (c.3205G>C) is associated with Inborn genetic diseases (ClinVar).

How common is LAMB3 p.Glu1069Gln (c.3205G>C) in the general population?

LAMB3 p.Glu1069Gln (c.3205G>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about LAMB3 p.Glu1069Gln (c.3205G>C)?

AlphaMissense predicts likely benign (score 0.0555) — an in-silico prediction, not a clinical call.

LAMB3 p.Glu1069Gln

c.3205G>C · VCV4046105

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0555	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.6	GERP -4.2
Regional constraint	o/e 0.97	unconstrained · MANE · 36 kb · p 0.27 · regional, not allelic
Overall
CADD	0.001	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,898 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,612,760 alleles · very rare exomes 5/1,460,538 · genomes 2/152,222 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,370
African / African-Americangrpmax	0.00134%	74,898
European (non-Finnish)	0.000424%	236,009

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu1069Gln
Coding: c.3205G>C
MANE Select: NM_000228
Type: single nucleotide variant
Location: chr1:209617433 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 1069: the 'domain i' region

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-glu1069gln (accessed [today's date]).

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