Is LAMB3 p.Val992fs (c.2975del) pathogenic?

LAMB3 p.Val992fs (c.2975del) is classified Pathogenic in LAMB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-08). Very rare (popmax 0.005%, amr).

How common is LAMB3 p.Val992fs (c.2975del) in the general population?

LAMB3 p.Val992fs (c.2975del) is very rare (popmax 0.005%, amr) (gnomAD).

LAMB3 p.Val992fs

c.2975del · rs770548526 · VCV2916145

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 20 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.52	GERP 0.49, phastCons 0.066

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,030 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,614,176 alleles · very rare exomes 3/1,461,874 · genomes 0/152,302 · 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.Val992fs
Coding: c.2975del
MANE Select: NM_000228
dbSNP: rs770548526
Type: Deletion
Location: chr1:209617983 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 992: the 'domain i' region

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

Similar variants

LAMB3 p.Val992= Likely benign ★ same residue
LAMB3 c.2685_2701+2del Likely pathogenic ★★ same type
LAMB3 c.2911_2938del Pathogenic/Likely pathogenic ★★ same type
LAMB3 p.Ala1055fs Pathogenic/Likely pathogenic ★★ same type
LAMB3 p.Ala832fs Pathogenic/Likely pathogenic ★★ same type
LAMB3 p.Asn456fs Pathogenic/Likely pathogenic ★★ same type
LAMB3 p.Cys325fs Likely pathogenic ★★ same type
LAMB3 p.Cys453fs Pathogenic/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-val992fs (accessed [today's date]).

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