Is LAMB1 p.Pro648= (c.1944C>T) pathogenic?

LAMB1 p.Pro648= (c.1944C>T) is classified Likely benign in LAMB1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-12). Ultra-rare (popmax 0.0493%, mid).

How common is LAMB1 p.Pro648= (c.1944C>T) in the general population?

LAMB1 p.Pro648= (c.1944C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

LAMB1 p.Pro648=

c.1944C>T · rs751175194 · VCV435722

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.6	GERP -4.3
Overall
CADD	0.359	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00136% 22/1,613,924 alleles · ultra-rare exomes 20/1,461,828 · genomes 2/152,096 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
African / African-American	0.00401%	24,962
Admixed American	0.00167%	59,990
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.0011%	90,767
South Asian	0.0011%	91,058

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.Pro648=
Coding: c.1944C>T
MANE Select: NM_002291
dbSNP: rs751175194
Type: single nucleotide variant
Location: chr7:107961590 (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.Pro648Ser Uncertain significance ★ 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-pro648 (accessed [today's date]).

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