Is LBR p.Ser182Phe (c.545C>T) pathogenic?

LBR p.Ser182Phe (c.545C>T) is classified Uncertain significance in LBR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). AlphaMissense: likely benign (0.0835); Very rare (popmax 0.00898%, nfe).

How common is LBR p.Ser182Phe (c.545C>T) in the general population?

LBR p.Ser182Phe (c.545C>T) is very rare (popmax 0.00898%, nfe) (gnomAD).

What do computational predictors say about LBR p.Ser182Phe (c.545C>T)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

LBR p.Ser182Phe

c.545C>T · rs370431555 · VCV2421051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00898%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -7.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.11	GERP -4.5
Regional constraint	o/e 0.94	unconstrained · MANE · 21 kb · p 0.12 · regional, not allelic
Overall
CADD	12.54	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 0.00898% European (non-Finnish) · 106/1,179,966 alleles

Filtering AF 0.00757% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00706%

Overall 0.00669% 108/1,613,972 alleles · very rare exomes 103/1,461,806 · genomes 5/152,166 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00898%	11,132
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00133%	74,918

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.Ser182Phe
Coding: c.545C>T
MANE Select: NM_002296
dbSNP: rs370431555
Type: single nucleotide variant
Location: chr1:225419358 (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 182: 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-ser182phe (accessed [today's date]).

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