Is PMP22 p.Arg159= (c.477C>T) pathogenic?

PMP22 p.Arg159= (c.477C>T) is classified Likely benign in PMP22 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-29). Very rare (popmax 0.005%, amr); Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with PMP22 p.Arg159= (c.477C>T)?

PMP22 p.Arg159= (c.477C>T) is associated with Charcot-Marie-Tooth disease type 1, Charcot-Marie-Tooth disease (ClinVar).

How common is PMP22 p.Arg159= (c.477C>T) in the general population?

PMP22 p.Arg159= (c.477C>T) is very rare (popmax 0.005%, amr) (gnomAD).

PMP22 p.Arg159=

c.477C>T · rs778132801 · VCV916813

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Charcot-Marie-Tooth disease type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.5
Overall
CADD	7.347	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,010 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00273% 44/1,613,822 alleles · very rare exomes 41/1,461,662 · genomes 3/152,160 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
South Asian	0.00329%	30,358
European (non-Finnish)	0.00305%	32,779
Remaining individualsnot grpmax-eligible	0.0016%	62,486
Finnishnot grpmax-eligible	0.00157%	63,840

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: PMP22
Protein: p.Arg159=
Coding: c.477C>T
MANE Select: NM_000304
dbSNP: rs778132801
Type: single nucleotide variant
Location: chr17:15230923 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 89.87

Full PMP22 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease

Similar variants

PMP22 p.Arg159Cys Uncertain significance ★★ ⚠ same residue
PMP22 p.Arg159His Uncertain significance ★★ ⚠ same residue
PMP22 p.Arg159Pro Uncertain significance ★ ⚠ same residue
PMP22 p.Ala67Pro Pathogenic/Likely pathogenic ★★ same condition
PMP22 p.Arg157Trp Pathogenic/Likely pathogenic ★★ same condition
PMP22 p.Cys109Ter Pathogenic ★★ same condition
PMP22 p.Gln103Ter Pathogenic ★★ same condition
PMP22 p.Gln86Ter 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/pmp22-p-arg159 (accessed [today's date]).

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