Is LMBRD2 p.Pro276Ser (c.826C>T) pathogenic?

LMBRD2 p.Pro276Ser (c.826C>T) is classified Uncertain significance in LMBRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely pathogenic (0.9025); Ultra-rare (popmax 0.0211%, amr); Associated with Inborn genetic diseases.

What condition is associated with LMBRD2 p.Pro276Ser (c.826C>T)?

LMBRD2 p.Pro276Ser (c.826C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LMBRD2 p.Pro276Ser (c.826C>T) in the general population?

LMBRD2 p.Pro276Ser (c.826C>T) is ultra-rare (popmax 0.0211%, amr) (gnomAD).

What do computational predictors say about LMBRD2 p.Pro276Ser (c.826C>T)?

AlphaMissense predicts likely pathogenic (score 0.9025) — an in-silico prediction, not a clinical call.

LMBRD2 p.Pro276Ser

c.826C>T · VCV3538636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9025 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0211%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9025	likely pathogenic
REVEL	0.418	indeterminate
SaProt	LLR -13.12	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 29 kb · p 2.3e-13 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.0211% Admixed American · 8/37,940 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00761%

Overall 0.000802% 12/1,495,970 alleles · ultra-rare exomes 8/1,349,136 · genomes 4/146,834 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0211%	4,743
Remaining individualsnot grpmax-eligible	0.00176%	56,978
European (non-Finnish)	0.000264%	378,505

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: LMBRD2
Protein: p.Pro276Ser
Coding: c.826C>T
MANE Select: NM_001007527
Type: single nucleotide variant
Location: chr5:36122958 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.95

Full LMBRD2 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

LMBRD2 p.Arg456His Uncertain significance ★★ ⚠ same condition
LMBRD2 p.Gln587Glu Uncertain significance ★★ ⚠ same condition
LMBRD2 p.Met224Thr Uncertain significance ★★ ⚠ same condition
LMBRD2 p.Thr611Ala Uncertain significance ★★ ⚠ same condition
LMBRD2 p.Ala41Ser Uncertain significance ★ ⚠ same condition
LMBRD2 p.Ala424Thr Uncertain significance ★ ⚠ same condition
LMBRD2 p.Ala464Val Uncertain significance ★ ⚠ same condition
LMBRD2 p.Ala471Gly 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/lmbrd2-p-pro276ser (accessed [today's date]).

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