Is LAMB3 p.Ser167Arg (c.501C>G) pathogenic?

LAMB3 p.Ser167Arg (c.501C>G) is classified Uncertain significance in LAMB3 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2024-07-10). AlphaMissense: likely benign (0.1697); Very rare (popmax 0.00161%, nfe); Associated with LAMB3-related disorder.

What condition is associated with LAMB3 p.Ser167Arg (c.501C>G)?

LAMB3 p.Ser167Arg (c.501C>G) is associated with LAMB3-related disorder (ClinVar).

How common is LAMB3 p.Ser167Arg (c.501C>G) in the general population?

LAMB3 p.Ser167Arg (c.501C>G) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about LAMB3 p.Ser167Arg (c.501C>G)?

AlphaMissense predicts likely benign (score 0.1697) — an in-silico prediction, not a clinical call.

LAMB3 p.Ser167Arg

c.501C>G · VCV3351955

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

LAMB3-related disorder

Computational evidence

Protein change
AlphaMissense	0.1697	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -8.35	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 3.8	GERP -0.85, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 36 kb · p 0.27 · regional, not allelic
Overall
CADD	16.54	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 0.00161% European (non-Finnish) · 19/1,180,030 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00124% 20/1,614,036 alleles · very rare exomes 14/1,461,894 · genomes 6/152,142 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,107
African / African-American	0.00133%	74,910

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.Ser167Arg
Coding: c.501C>G
MANE Select: NM_000228
Type: single nucleotide variant
Location: chr1:209634510 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 167: the laminin n-terminal domain

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

Disease context

LAMB3-related disorder

Similar variants

LAMB3 c.3383-1G>A Pathogenic/Likely pathogenic ★★ same condition
LAMB3 c.823-2A>C Pathogenic/Likely pathogenic ★★ same condition
LAMB3 p.Arg42Ter Pathogenic ★★ same condition
LAMB3 p.Arg569Ter Pathogenic ★★ same condition
LAMB3 p.Arg635Ter Pathogenic ★★ same condition
LAMB3 p.Gln117Ter Pathogenic/Likely pathogenic ★★ same condition
LAMB3 p.Met1Ile Likely pathogenic ★★ same condition
LAMB3 p.Ser167fs Pathogenic ★★ same residue

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-ser167arg (accessed [today's date]).

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