Is MOBP p.Pro87Leu (c.260C>T) pathogenic?

MOBP p.Pro87Leu (c.260C>T) is classified Uncertain significance in MOBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-06). AlphaMissense: likely benign (0.1419); Ultra-rare (popmax 0.0166%, mid); Associated with MOBP-related disorder.

What condition is associated with MOBP p.Pro87Leu (c.260C>T)?

MOBP p.Pro87Leu (c.260C>T) is associated with MOBP-related disorder (ClinVar).

How common is MOBP p.Pro87Leu (c.260C>T) in the general population?

MOBP p.Pro87Leu (c.260C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about MOBP p.Pro87Leu (c.260C>T)?

AlphaMissense predicts likely benign (score 0.1419) — an in-silico prediction, not a clinical call.

MOBP p.Pro87Leu

c.260C>T · rs781467178 · VCV2636755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1419 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MOBP-related disorder

Computational evidence

Protein change
AlphaMissense	0.1419	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -9.65	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 3.6	GERP -1.1, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 710 bp · p 4.9e-08 · regional, not allelic
Overall
CADD	23.2	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 0.0166% Middle Eastern · 1/6,024 alleles

Filtering AF 0.00209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00185%

Overall 0.00235% 37/1,572,838 alleles · ultra-rare exomes 32/1,420,632 · genomes 5/152,206 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,024
European (non-Finnish)	0.00291%	34,372
East Asian	0.00231%	43,268
Admixed American	0.00179%	55,732

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: MOBP
Protein: p.Pro87Leu
Coding: c.260C>T
MANE Select: NM_001393704
dbSNP: rs781467178
Type: single nucleotide variant
Location: chr3:39502588 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 55.69
Residue 87: the 'disordered' region

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

Disease context

MOBP-related disorder

Similar variants

MOBP c.206+5G>C Uncertain significance ★ same condition
MOBP p.Pro84Ser Uncertain significance ★ ⚠ same condition
MOBP c.207-27G>A Likely benign ★ same condition
MOBP c.207-22C>T Uncertain significance same condition
MOBP p.Lys96= Likely benign same condition
MOBP p.Pro121Ser Likely benign ⚠ same condition
MOBP p.Pro152= Likely benign same condition
MOBP p.Pro80= Likely benign 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/mobp-p-pro87leu (accessed [today's date]).

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