Is MPZ p.Arg106Pro (c.317G>C) pathogenic?

MPZ p.Arg106Pro (c.317G>C) is classified Uncertain significance in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-01). AlphaMissense: likely pathogenic (0.5708); Very rare (popmax 0.000169%, nfe).

How common is MPZ p.Arg106Pro (c.317G>C) in the general population?

MPZ p.Arg106Pro (c.317G>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about MPZ p.Arg106Pro (c.317G>C)?

AlphaMissense predicts likely pathogenic (score 0.5708) — an in-silico prediction, not a clinical call.

MPZ p.Arg106Pro

c.317G>C · rs145039212 · VCV805018

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5708 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5708	likely pathogenic
REVEL	0.197	benign-leaning
SaProt	LLR -7.68	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.21	GERP -3.7, phastCons 0.23
Regional constraint	o/e 0.69	unconstrained · MANE · 3,519 bp · p 4.1e-06 · regional, not allelic
Overall
CADD	15.52	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 0.000169% European (non-Finnish) · 2/1,179,948 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,896 alleles · very rare exomes 2/1,461,842 · genomes 0/152,054 · 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: MPZ
Protein: p.Arg106Pro
Coding: c.317G>C
MANE Select: NM_000530
dbSNP: rs145039212
Type: single nucleotide variant
Location: chr1:161306839 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 106: an α-helix; the ig-like v-type domain

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

Similar variants

MPZ p.Arg106His Uncertain significance ★★ ⚠ same residue
MPZ p.Arg106Cys Conflicting classifications of pathogenicity ★ same residue
MPZ c.235-1G>T Pathogenic/Likely pathogenic ★★ same type
MPZ c.448+1G>A Pathogenic/Likely pathogenic ★★ same type
MPZ c.448+1G>T Likely pathogenic ★★ same type
MPZ c.448+2T>G Likely pathogenic ★★ same type
MPZ c.584+2T>G Pathogenic ★★ same type
MPZ c.68-1G>A Pathogenic/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/mpz-p-arg106pro (accessed [today's date]).

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