Is MPZ p.Ser233Arg (c.699T>G) pathogenic?

MPZ p.Ser233Arg (c.699T>G) is classified Likely pathogenic in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2016-01-01). AlphaMissense: likely pathogenic (0.6865); Absent from gnomAD v4.1; Associated with Roussy-Levy syndrome.

What condition is associated with MPZ p.Ser233Arg (c.699T>G)?

MPZ p.Ser233Arg (c.699T>G) is associated with Roussy-Levy syndrome (ClinVar).

How common is MPZ p.Ser233Arg (c.699T>G) in the general population?

MPZ p.Ser233Arg (c.699T>G) is absent from gnomAD v4.1 (gnomAD).

How is Roussy-Lévy syndrome inherited?

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

What do computational predictors say about MPZ p.Ser233Arg (c.699T>G)?

AlphaMissense predicts likely pathogenic (score 0.6865) — an in-silico prediction, not a clinical call.

MPZ p.Ser233Arg

c.699T>G · rs1057518839 · VCV374017

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6865 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Roussy-Levy syndrome

Computational evidence

Protein change
AlphaMissense	0.6865	likely pathogenic ✓ concordant with ClinVar
REVEL	0.585	indeterminate
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.5	GERP -3.4
Regional constraint	o/e 1.08	unconstrained · MANE · 506 bp · p 0.45 · regional, not allelic
Overall
CADD	14.23	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MPZ
Protein: p.Ser233Arg
Coding: c.699T>G
MANE Select: NM_000530
dbSNP: rs1057518839
Type: single nucleotide variant
Location: chr1:161305924 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 233: a modified residue (phosphoserine; by pkc); the 'disordered' region; a UniProt-annotated variant site (in chn2)

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

Disease context

Roussy-Levy syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Roussy-Lévy syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy

Similar variants

MPZ p.Asn131Lys Pathogenic ★★ ⚠ same condition
MPZ p.Gly167Arg Pathogenic ★★ same condition
MPZ p.Pro133Ala Likely pathogenic ★★ same condition
MPZ p.Pro133Thr Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Ser233fs Pathogenic/Likely pathogenic ★★ same residue
MPZ p.Thr124Met Pathogenic ★★ same condition
MPZ p.Tyr145Ser Pathogenic ★★ ⚠ same condition
MPZ p.Thr143Met 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/mpz-p-ser233arg (accessed [today's date]).

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