Is MOBP p.Pro121Ser (c.361C>T) pathogenic?

MOBP p.Pro121Ser (c.361C>T) is classified Likely benign in MOBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-12). AlphaMissense: likely benign (0.143); Very rare (popmax 0.00644%, nfe); Associated with MOBP-related disorder.

What condition is associated with MOBP p.Pro121Ser (c.361C>T)?

MOBP p.Pro121Ser (c.361C>T) is associated with MOBP-related disorder (ClinVar).

How common is MOBP p.Pro121Ser (c.361C>T) in the general population?

MOBP p.Pro121Ser (c.361C>T) is very rare (popmax 0.00644%, nfe) (gnomAD).

What do computational predictors say about MOBP p.Pro121Ser (c.361C>T)?

AlphaMissense predicts likely benign (score 0.143) — an in-silico prediction, not a clinical call.

MOBP p.Pro121Ser

c.361C>T · rs995835006 · VCV2634225

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.143 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00644%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MOBP-related disorder

Computational evidence

Protein change
AlphaMissense	0.143	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -11.02	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.41	GERP 0.24, phastCons 0.99
Regional constraint	o/e 0.63	unconstrained · MANE · 710 bp · p 4.9e-08 · regional, not allelic
Overall
CADD	13.26	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 0.00644% European (non-Finnish) · 73/1,133,550 alleles

Filtering AF 0.00523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00481%

Overall 0.00563% 85/1,509,248 alleles · very rare exomes 76/1,357,436 · genomes 9/151,812 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0136%	7,364
European (non-Finnish)grpmax	0.00644%	15,528
Admixed American	0.00416%	24,033
African / African-American	0.00276%	36,242

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro121Ser
Coding: c.361C>T
MANE Select: NM_001393704
dbSNP: rs995835006
Type: single nucleotide variant
Location: chr3:39502689 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 55.69
Residue 121: the 'disordered' region; the '4 x 10 aa tandem repeats of p-r-s-p-p-r-s-e-r-q' 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 p.Pro87Leu 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.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-pro121ser (accessed [today's date]).

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