Is LAMB1 p.Pro648Ser (c.1942C>T) pathogenic?

LAMB1 p.Pro648Ser (c.1942C>T) is classified Uncertain significance in LAMB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). AlphaMissense: ambiguous (0.3665); Very rare (popmax 8.47e-05%, nfe).

How common is LAMB1 p.Pro648Ser (c.1942C>T) in the general population?

LAMB1 p.Pro648Ser (c.1942C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about LAMB1 p.Pro648Ser (c.1942C>T)?

AlphaMissense predicts ambiguous (score 0.3665) — an in-silico prediction, not a clinical call.

LAMB1 p.Pro648Ser

c.1942C>T · rs2033502766 · VCV1714689

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3665 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3665	ambiguous
REVEL	0.368	indeterminate
SaProt	LLR -5.29	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 79 kb · p 0.15 · regional, not allelic
Overall
CADD	25.2	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 8.47e-05% European (non-Finnish) · 1/1,179,980 alleles

Overall 6.2e-05% 1/1,614,070 alleles · very rare exomes 1/1,461,836 · genomes 0/152,234 · 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: LAMB1
Protein: p.Pro648Ser
Coding: c.1942C>T
MANE Select: NM_002291
dbSNP: rs2033502766
Type: single nucleotide variant
Location: chr7:107961592 (GRCh38)
Gene constraint: LOEUF 0.601 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.99 · 3 PDB
Residue 648: the laminin iv type b domain

Full LAMB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LAMB1 p.Pro648= Likely benign ★★ same residue
LAMB1 p.Pro648Thr Uncertain significance ★ ⚠ same residue
LAMB1 c.4188+1G>C Pathogenic/Likely pathogenic ★★ same type
LAMB1 p.Arg397Ter Pathogenic ★★ same type
LAMB1 p.Gln577Ter Pathogenic ★★ same type
LAMB1 c.1985+5G>T Uncertain significance ★★ same type
LAMB1 c.4746-3C>A Uncertain significance ★★ same type
LAMB1 p.Ala1069Val Uncertain significance ★★ ⚠ 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/lamb1-p-pro648ser (accessed [today's date]).

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