Is LMBRD2 p.Ser672Phe (c.2015C>T) pathogenic?

LMBRD2 p.Ser672Phe (c.2015C>T) is classified Uncertain significance in LMBRD2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-29). AlphaMissense: likely benign (0.1232); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with LMBRD2 p.Ser672Phe (c.2015C>T)?

LMBRD2 p.Ser672Phe (c.2015C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LMBRD2 p.Ser672Phe (c.2015C>T) in the general population?

LMBRD2 p.Ser672Phe (c.2015C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about LMBRD2 p.Ser672Phe (c.2015C>T)?

AlphaMissense predicts likely benign (score 0.1232) — an in-silico prediction, not a clinical call.

LMBRD2 p.Ser672Phe

c.2015C>T · rs1743432197 · VCV2211265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1232 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1232	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 10 kb · p 0.66 · regional, not allelic
Overall
CADD	23.4	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 0.00167% Admixed American · 1/59,870 alleles

Overall 6.2e-05% 1/1,612,220 alleles · very rare exomes 0/1,460,172 · genomes 1/152,048 · joint denominator

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.Ser672Phe
Coding: c.2015C>T
MANE Select: NM_001007527
dbSNP: rs1743432197
Type: single nucleotide variant
Location: chr5:36105080 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.95
Residue 672: the 'disordered' region

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-ser672phe (accessed [today's date]).

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