Is MOBP p.Arg172Ser (c.514C>A) pathogenic?

MOBP p.Arg172Ser (c.514C>A) is classified Uncertain significance in MOBP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-09). AlphaMissense: likely pathogenic (0.5942); Very rare (popmax 0.00153%, nfe); Associated with amyotrophic lateral sclerosis.

What condition is associated with MOBP p.Arg172Ser (c.514C>A)?

MOBP p.Arg172Ser (c.514C>A) is associated with amyotrophic lateral sclerosis (ClinVar).

How common is MOBP p.Arg172Ser (c.514C>A) in the general population?

MOBP p.Arg172Ser (c.514C>A) is very rare (popmax 0.00153%, nfe) (gnomAD).

How is Amyotrophic lateral sclerosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MOBP p.Arg172Ser (c.514C>A)?

AlphaMissense predicts likely pathogenic (score 0.5942) — an in-silico prediction, not a clinical call.

MOBP p.Arg172Ser

c.514C>A · rs1188260744 · VCV981023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

amyotrophic lateral sclerosis

Computational evidence

Protein change
AlphaMissense	0.5942	likely pathogenic
REVEL	0.093	moderately benign-leaning
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 96 bp · p 0.15 · regional, not allelic
Overall
CADD	23.7	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 0.00153% European (non-Finnish) · 17/1,108,922 alleles

Filtering AF 0.000934% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000763%

Overall 0.00114% 17/1,485,384 alleles · very rare exomes 17/1,333,034 · genomes 0/152,350 · 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: MOBP
Protein: p.Arg172Ser
Coding: c.514C>A
MANE Select: NM_001393704
dbSNP: rs1188260744
Type: single nucleotide variant
Location: chr3:39502842 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 55.69
Residue 172: the 'disordered' region

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

Disease context

amyotrophic lateral sclerosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Amyotrophic lateral sclerosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

MOBP c.206+5G>C Uncertain significance ★ same type
MOBP p.Ala64Thr Uncertain significance ★ same type
MOBP p.Ala6Thr Uncertain significance ★ ⚠ same type
MOBP p.Gly9Cys Uncertain significance ★ ⚠ same type
MOBP p.Phe22Leu Uncertain significance ★ ⚠ same type
MOBP p.Phe30Leu Uncertain significance ★ ⚠ same type
MOBP p.Pro76Arg Uncertain significance ★ same type
MOBP p.Pro84Ser Uncertain significance ★ ⚠ 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/mobp-p-arg172ser (accessed [today's date]).

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