Is LBR p.Ser306Pro (c.916T>C) pathogenic?

LBR p.Ser306Pro (c.916T>C) is classified Uncertain significance in LBR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-19). AlphaMissense: likely pathogenic (0.6123); Absent from gnomAD v4.1.

How common is LBR p.Ser306Pro (c.916T>C) in the general population?

LBR p.Ser306Pro (c.916T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LBR p.Ser306Pro (c.916T>C)?

AlphaMissense predicts likely pathogenic (score 0.6123) — an in-silico prediction, not a clinical call.

LBR p.Ser306Pro

c.916T>C · rs2527798907 · VCV2433417

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6123 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6123	likely pathogenic
REVEL	0.591	indeterminate
SaProt	LLR -10.48	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP -4.9, phastCons 0.043
Regional constraint	o/e 0.94	unconstrained · MANE · 21 kb · p 0.12 · regional, not allelic
Overall
CADD	16.93	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Ser306Pro
Coding: c.916T>C
MANE Select: NM_002296
dbSNP: rs2527798907
Type: single nucleotide variant
Location: chr1:225412622 (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 306: 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.Ser306= Likely benign ★★ same residue
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

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-ser306pro (accessed [today's date]).

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