Is LBR p.Pro352His (c.1055C>A) pathogenic?

LBR p.Pro352His (c.1055C>A) is classified Uncertain significance in LBR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). AlphaMissense: likely benign (0.0991); Absent from gnomAD v4.1.

How common is LBR p.Pro352His (c.1055C>A) in the general population?

LBR p.Pro352His (c.1055C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LBR p.Pro352His (c.1055C>A)?

AlphaMissense predicts likely benign (score 0.0991) — an in-silico prediction, not a clinical call.

LBR p.Pro352His

c.1055C>A · VCV4746555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0991	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -7.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.84, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 21 kb · p 0.12 · regional, not allelic
Overall
CADD	16.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LBR
Protein: p.Pro352His
Coding: c.1055C>A
MANE Select: NM_002296
Type: single nucleotide variant
Location: chr1:225412483 (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 352: a UniProt-annotated variant site (in skpha)

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

Similar variants

LBR c.367-2A>C Pathogenic/Likely pathogenic ★★ same type
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-pro352his (accessed [today's date]).

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