Is LDB3 p.Ser367Pro (c.1099T>C) pathogenic?

LDB3 p.Ser367Pro (c.1099T>C) is classified Uncertain significance in LDB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely benign (0.074); Ultra-rare (popmax 0.017%, mid); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Ser367Pro (c.1099T>C)?

LDB3 p.Ser367Pro (c.1099T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is LDB3 p.Ser367Pro (c.1099T>C) in the general population?

LDB3 p.Ser367Pro (c.1099T>C) is ultra-rare (popmax 0.017%, mid) (gnomAD).

What do computational predictors say about LDB3 p.Ser367Pro (c.1099T>C)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

LDB3 p.Ser367Pro

c.1099T>C · VCV3537668

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -7.32	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 1.6	GERP -2.9, phastCons 0.94
Regional constraint	o/e 0.95	unconstrained · MANE · 64 kb · p 0.14 · regional, not allelic
Overall
CADD	16.99	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 0.017% Middle Eastern · 1/5,880 alleles

Overall 0.000124% 2/1,611,244 alleles · ultra-rare exomes 2/1,458,996 · genomes 0/152,248 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.017%	5,880
European (non-Finnish)	8.48e-05%	1,179,930

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: LDB3
Protein: p.Ser367Pro
Coding: c.1099T>C
MANE Select: NM_007078
Type: single nucleotide variant
Location: chr10:86709918 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 367: the 'disordered' region

Full LDB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LDB3 c.246-3C>T Uncertain significance ★★ same condition
LDB3 c.860-3C>T Uncertain significance ★★ same condition
LDB3 p.Ala119Val Uncertain significance ★★ ⚠ same condition
LDB3 p.Ala126Val Uncertain significance ★★ ⚠ same condition
LDB3 p.Ala248Thr Uncertain significance ★★ same condition
LDB3 p.Ala264Thr Uncertain significance ★★ ⚠ same condition
LDB3 p.Ala365Asp Uncertain significance ★★ ⚠ same condition
LDB3 p.Ala365Val 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/ldb3-p-ser367pro (accessed [today's date]).

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