Is MPV17 p.Pro64Ser (c.190C>T) pathogenic?

MPV17 p.Pro64Ser (c.190C>T) is classified Conflicting classifications of pathogenicity in MPV17 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-07-20). AlphaMissense: likely pathogenic (0.7676); Very rare (popmax 0.00329%, sas); Associated with Charcot-Marie-Tooth disease, axonal, type 2EE.

What condition is associated with MPV17 p.Pro64Ser (c.190C>T)?

MPV17 p.Pro64Ser (c.190C>T) is associated with Charcot-Marie-Tooth disease, axonal, type 2EE (ClinVar).

How common is MPV17 p.Pro64Ser (c.190C>T) in the general population?

MPV17 p.Pro64Ser (c.190C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about MPV17 p.Pro64Ser (c.190C>T)?

AlphaMissense predicts likely pathogenic (score 0.7676) — an in-silico prediction, not a clinical call.

MPV17 p.Pro64Ser

c.190C>T · rs2465683495 · VCV2026719

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7676 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease, axonal, type 2EE

Computational evidence

Protein change
AlphaMissense	0.7676	likely pathogenic
REVEL	0.883	moderately pathogenic-leaning
SaProt	LLR -11.06	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	27.2	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 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000248% 4/1,613,994 alleles · very rare exomes 4/1,461,676 · genomes 0/152,318 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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: MPV17
Protein: p.Pro64Ser
Coding: c.190C>T
MANE Select: NM_002437
dbSNP: rs2465683495
Type: single nucleotide variant
Location: chr2:27312769 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.23
Residue 64: a UniProt-annotated variant site (in mtdps6)

Full MPV17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease, axonal, type 2EE — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPV17 p.Pro64Arg Pathogenic/Likely pathogenic ★★ same residue
MPV17 p.Pro64Leu Likely pathogenic ★ same residue
MPV17 c.186+2T>C Pathogenic/Likely pathogenic ★★ same condition
MPV17 c.375+1G>A Likely pathogenic ★★ same condition
MPV17 c.375+1G>T Likely pathogenic ★★ same condition
MPV17 c.375+2T>C Likely pathogenic ★★ same condition
MPV17 c.376-2A>C Pathogenic/Likely pathogenic ★★ same condition
MPV17 c.408+1G>A Pathogenic/Likely pathogenic ★★ 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/mpv17-p-pro64ser (accessed [today's date]).

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