Is LBR p.Val581fs (c.1741_1742del) pathogenic?

LBR p.Val581fs (c.17411742del) is classified Pathogenic in LBR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). No gnomAD frequency available for this variant.

How common is LBR p.Val581fs (c.1741_1742del) in the general population?

LBR p.Val581fs (c.1741_1742del) is no gnomAD frequency available for this variant (gnomAD).

LBR p.Val581fs

c.1741_1742del · rs2150942257 · VCV1390897

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (14 of 14) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.42	GERP -5.3, phastCons 0.012

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LBR
Protein: p.Val581fs
Coding: c.1741_1742del
MANE Select: NM_002296
dbSNP: rs2150942257
Type: Deletion
Location: chr1:225403409 (GRCh38)
Gene constraint: LOEUF 0.499 · pLI 0.97 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.89 · 1 PDB
Residue 581: a UniProt-annotated variant site (in skpha)

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

Similar variants

LBR p.Val581Ile Uncertain significance ★ ⚠ same residue
LBR c.893-5del Benign/Likely benign ★★ same type
LBR p.Tyr474fs Likely pathogenic ★ same type
LBR c.1483+3_1483+6del Uncertain significance ★ same type
LBR p.Ser86_Arg89del Uncertain significance ★ same type
LBR p.Val281del Uncertain significance ★ same type
LBR c.450+41del Likely benign ★ same type
LBR c.640+13del Likely benign ★ 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/lbr-p-val581fs (accessed [today's date]).

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