Is LAMB3 p.Ala596Ser (c.1786G>T) pathogenic?

LAMB3 p.Ala596Ser (c.1786G>T) is classified Conflicting classifications of pathogenicity in LAMB3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.0748); Rare (popmax 0.108%, sas); Associated with Inborn genetic diseases.

What condition is associated with LAMB3 p.Ala596Ser (c.1786G>T)?

LAMB3 p.Ala596Ser (c.1786G>T) is associated with Inborn genetic diseases (ClinVar).

How common is LAMB3 p.Ala596Ser (c.1786G>T) in the general population?

LAMB3 p.Ala596Ser (c.1786G>T) is rare (popmax 0.108%, sas) (gnomAD).

What do computational predictors say about LAMB3 p.Ala596Ser (c.1786G>T)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

LAMB3 p.Ala596Ser

c.1786G>T · rs374016408 · VCV765869

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.108%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -4.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP -1.6, phastCons 0.039
Regional constraint	o/e 0.97	unconstrained · MANE · 36 kb · p 0.27 · regional, not allelic
Overall
CADD	7.528	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 0.108% South Asian · 98/91,080 alleles

Filtering AF 0.0903% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0839%

Overall 0.00638% 103/1,613,990 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.108%	929
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00133%	74,944
European (non-Finnish)	8.47e-05%	1,180,013

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.Ala596Ser
Coding: c.1786G>T
MANE Select: NM_000228
dbSNP: rs374016408
Type: single nucleotide variant
Location: chr1:209625838 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 596: the 'domain ii' 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.Ala596Pro Uncertain significance ★ ⚠ same residue
LAMB3 p.Ala596Val 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-ala596ser (accessed [today's date]).

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