Is LAMB3 p.Arg569Pro (c.1706G>C) pathogenic?

LAMB3 p.Arg569Pro (c.1706G>C) is classified Uncertain significance in LAMB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-16). AlphaMissense: likely benign (0.1994); Very rare (popmax 0.00834%, amr); Associated with Inborn genetic diseases.

What condition is associated with LAMB3 p.Arg569Pro (c.1706G>C)?

LAMB3 p.Arg569Pro (c.1706G>C) is associated with Inborn genetic diseases (ClinVar).

How common is LAMB3 p.Arg569Pro (c.1706G>C) in the general population?

LAMB3 p.Arg569Pro (c.1706G>C) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about LAMB3 p.Arg569Pro (c.1706G>C)?

AlphaMissense predicts likely benign (score 0.1994) — an in-silico prediction, not a clinical call.

LAMB3 p.Arg569Pro

c.1706G>C · VCV3290019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1994	likely benign
REVEL	0.44	indeterminate
SaProt	LLR -3.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.99, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 36 kb · p 0.27 · regional, not allelic
Overall
CADD	27.5	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 0.00834% Admixed American · 5/59,984 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000744% 12/1,613,814 alleles · very rare exomes 12/1,461,468 · genomes 0/152,346 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,997
European (non-Finnish)	0.000593%	168,556

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.Arg569Pro
Coding: c.1706G>C
MANE Select: NM_000228
Type: single nucleotide variant
Location: chr1:209625918 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 569: the laminin egf-like 6 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.Arg569Ter Pathogenic ★★ same residue
LAMB3 p.Arg569Gln Uncertain significance ★ ⚠ same residue
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

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-arg569pro (accessed [today's date]).

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