Is LBR p.Pro358Ser (c.1072C>T) pathogenic?

LBR p.Pro358Ser (c.1072C>T) is classified Uncertain significance in LBR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-11). AlphaMissense: likely benign (0.085); Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with LBR p.Pro358Ser (c.1072C>T)?

LBR p.Pro358Ser (c.1072C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LBR p.Pro358Ser (c.1072C>T) in the general population?

LBR p.Pro358Ser (c.1072C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about LBR p.Pro358Ser (c.1072C>T)?

AlphaMissense predicts likely benign (score 0.085) — an in-silico prediction, not a clinical call.

LBR p.Pro358Ser

c.1072C>T · rs145328578 · VCV1426469

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.085 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.085	likely benign
REVEL	0.311	indeterminate
SaProt	LLR -5.22	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 8.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 21 kb · p 0.12 · regional, not allelic
Overall
CADD	18.69	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

Grpmax group 0.00667% Admixed American · 4/59,998 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00161% 26/1,613,904 alleles · very rare exomes 25/1,461,766 · genomes 1/152,138 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,999
European (non-Finnish)	0.00186%	53,635

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.Pro358Ser
Coding: c.1072C>T
MANE Select: NM_002296
dbSNP: rs145328578
Type: single nucleotide variant
Location: chr1:225412466 (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 358: a UniProt-annotated variant site (in skpha)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LBR p.Ala109Gly Uncertain significance ★★ ⚠ same condition
LBR p.Ala434Ser Uncertain significance ★★ ⚠ same condition
LBR p.Arg169His Uncertain significance ★★ ⚠ same condition
LBR p.Arg347Cys Uncertain significance ★★ ⚠ same condition
LBR p.Arg347His Uncertain significance ★★ ⚠ same condition
LBR p.Arg372His Uncertain significance ★★ ⚠ same condition
LBR p.Arg544Cys Uncertain significance ★★ ⚠ same condition
LBR p.Arg544His Uncertain significance ★★ ⚠ same condition

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-pro358ser (accessed [today's date]).

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