Is LBR p.Ser306= (c.918T>G) pathogenic?

LBR p.Ser306= (c.918T>G) is classified Likely benign in LBR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-18). Very rare (popmax 0.00815%, nfe).

How common is LBR p.Ser306= (c.918T>G) in the general population?

LBR p.Ser306= (c.918T>G) is very rare (popmax 0.00815%, nfe) (gnomAD).

LBR p.Ser306=

c.918T>G · rs767893490 · VCV762449

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00815%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -5.3
Overall
CADD	1.964	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00815% European (non-Finnish) · 96/1,178,288 alleles

Filtering AF 0.00682% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00726% 117/1,611,842 alleles · very rare exomes 104/1,459,924 · genomes 13/151,918 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0281%	3,553
European (non-Finnish)grpmax	0.00815%	12,274
African / African-American	0.00268%	37,376
Remaining individualsnot grpmax-eligible	0.0016%	62,408

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser306=
Coding: c.918T>G
MANE Select: NM_002296
dbSNP: rs767893490
Type: single nucleotide variant
Location: chr1:225412620 (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.Ser306Pro Uncertain significance ★ ⚠ 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-ser306 (accessed [today's date]).

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