Is LBR p.Arg89Ter (c.265C>T) pathogenic?

LBR p.Arg89Ter (c.265C>T) is classified Pathogenic in LBR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Very rare (popmax 0.0011%, sas).

How common is LBR p.Arg89Ter (c.265C>T) in the general population?

LBR p.Arg89Ter (c.265C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

LBR p.Arg89Ter

c.265C>T · VCV4803593

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 14
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8	GERP 1.8, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,066 alleles

Overall 0.000124% 2/1,613,422 alleles · very rare exomes 2/1,461,172 · genomes 0/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,066
European (non-Finnish)	8.48e-05%	1,179,485

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: LBR
Protein: p.Arg89Ter
Coding: c.265C>T
MANE Select: NM_002296
Type: single nucleotide variant
Location: chr1:225422178 (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 89: the 'disordered' region; a UniProt-annotated variant site (in skpha)

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

Similar variants

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LBR p.Arg512Gln Pathogenic/Likely pathogenic ★★ same type
LBR p.Arg583Gln Pathogenic ★★ same type
LBR p.Arg586His Pathogenic/Likely pathogenic ★★ same type
LBR p.Asn547Asp Pathogenic/Likely pathogenic ★★ same type
LBR p.Asn547Ser Pathogenic/Likely pathogenic ★★ same type
LBR c.*1586G>A Uncertain significance ★★ same type
LBR p.Ala109Gly 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/lbr-p-arg89ter (accessed [today's date]).

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