Is LAMB3 p.Lys188Glu (c.562A>G) pathogenic?

LAMB3 p.Lys188Glu (c.562A>G) is classified Uncertain significance in LAMB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1201); Very rare (popmax 0.000593%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LAMB3 p.Lys188Glu (c.562A>G)?

LAMB3 p.Lys188Glu (c.562A>G) is associated with Inborn genetic diseases (ClinVar).

How common is LAMB3 p.Lys188Glu (c.562A>G) in the general population?

LAMB3 p.Lys188Glu (c.562A>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about LAMB3 p.Lys188Glu (c.562A>G)?

AlphaMissense predicts likely benign (score 0.1201) — an in-silico prediction, not a clinical call.

LAMB3 p.Lys188Glu

c.562A>G · VCV4828776

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1201 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1201	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	donor loss, 2 bp away · masked 0 · deltas
Pangolin	Δ0.24	loss · gain 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 36 kb · p 0.27 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,820 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,542 alleles · very rare exomes 4/1,461,744 · genomes 3/151,798 · joint denominator

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.Lys188Glu
Coding: c.562A>G
MANE Select: NM_000228
Type: single nucleotide variant
Location: chr1:209634449 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 188: the laminin n-terminal 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

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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-lys188glu (accessed [today's date]).

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