Is LAMB3 p.Pro158Ser (c.472C>T) pathogenic?

LAMB3 p.Pro158Ser (c.472C>T) is classified Uncertain significance in LAMB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-08). AlphaMissense: likely benign (0.1349); Very rare (popmax 0.00669%, eas).

How common is LAMB3 p.Pro158Ser (c.472C>T) in the general population?

LAMB3 p.Pro158Ser (c.472C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about LAMB3 p.Pro158Ser (c.472C>T)?

AlphaMissense predicts likely benign (score 0.1349) — an in-silico prediction, not a clinical call.

LAMB3 p.Pro158Ser

c.472C>T · VCV4744302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1349 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1349	likely benign
REVEL	0.72	pathogenic-leaning
SaProt	LLR -7.48	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 36 kb · p 0.27 · regional, not allelic
Overall
CADD	25.0	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 0.00669% East Asian · 3/44,868 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000186% 3/1,614,044 alleles · very rare exomes 2/1,461,888 · genomes 1/152,156 · 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.Pro158Ser
Coding: c.472C>T
MANE Select: NM_000228
Type: single nucleotide variant
Location: chr1:209634539 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 158: the laminin n-terminal domain

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

Similar variants

LAMB3 c.1132+5G>A Pathogenic/Likely pathogenic ★★ same type
LAMB3 c.1133-22G>A Pathogenic ★★ same type
LAMB3 c.1288+1G>T Pathogenic/Likely pathogenic ★★ same type
LAMB3 c.1486-1G>A Likely pathogenic ★★ same type
LAMB3 c.1597+1G>T Likely pathogenic ★★ same type
LAMB3 c.2138-1G>A Likely pathogenic ★★ same type
LAMB3 c.2701+2T>C Likely pathogenic ★★ same type
LAMB3 c.28+1G>T Likely pathogenic ★★ same type

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-pro158ser (accessed [today's date]).

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