Is LDB1 p.Pro31Arg (c.92C>G) pathogenic?

LDB1 p.Pro31Arg (c.92C>G) is classified Uncertain significance in LDB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: ambiguous (0.562); Ultra-rare (popmax 0.0171%, mid).

How common is LDB1 p.Pro31Arg (c.92C>G) in the general population?

LDB1 p.Pro31Arg (c.92C>G) is ultra-rare (popmax 0.0171%, mid) (gnomAD).

What do computational predictors say about LDB1 p.Pro31Arg (c.92C>G)?

AlphaMissense predicts ambiguous (score 0.562) — an in-silico prediction, not a clinical call.

LDB1 p.Pro31Arg

c.92C>G · VCV4546078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.562 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, mid)

Computational evidence

Protein change
AlphaMissense	0.562	ambiguous
REVEL	0.328	indeterminate
SaProt	LLR -7.11	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 218 bp · p 0.54 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0171% Middle Eastern · 1/5,850 alleles

Filtering AF 0.00365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.0023% 36/1,567,032 alleles · ultra-rare exomes 31/1,414,840 · genomes 5/152,192 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0171%	5,850
Admixed American	0.00927%	10,793
East Asian	0.00676%	14,801
African / African-American	0.00408%	24,528
Ashkenazi Jewishnot grpmax-eligible	0.0038%	26,330
South Asian	0.00237%	42,117
European (non-Finnish)	0.00173%	57,760
Remaining individualsnot grpmax-eligible	0.00166%	60,356

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: LDB1
Protein: p.Pro31Arg
Coding: c.92C>G
MANE Select: NM_001113407
Type: single nucleotide variant
Location: chr10:102111470 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.04 · 9 PDB

Full LDB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LDB1 p.Pro31Leu Uncertain significance ★ ⚠ same residue
LDB1 c.733-1G>T Pathogenic ★ same type
LDB1 p.Arg121Trp Likely pathogenic ★ same type
LDB1 p.Arg193Trp Likely pathogenic ★ same type
LDB1 p.Gln203Ter Likely pathogenic ★ same type
LDB1 p.Gln333Ter Pathogenic ★ same type
LDB1 p.Gln66Ter Pathogenic ★ same type
LDB1 p.Thr359Pro Likely pathogenic ★ 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/ldb1-p-pro31arg (accessed [today's date]).

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