Is PMP22 p.Val141= (c.423G>T) pathogenic?

PMP22 p.Val141= (c.423G>T) is classified Likely benign in PMP22 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-08). Ultra-rare (popmax 0.0507%, afr); Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with PMP22 p.Val141= (c.423G>T)?

PMP22 p.Val141= (c.423G>T) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is PMP22 p.Val141= (c.423G>T) in the general population?

PMP22 p.Val141= (c.423G>T) is ultra-rare (popmax 0.0507%, afr) (gnomAD).

PMP22 p.Val141=

c.423G>T · rs144077495 · VCV705336

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0507%, afr)

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 1.8	GERP 0.87, phastCons 1
Overall
CADD	7.652	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0507% African / African-American · 38/74,916 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0335%

Overall 0.00248% 40/1,614,038 alleles · ultra-rare exomes 12/1,461,854 · genomes 28/152,184 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0507%	1,971
Admixed American	0.00167%	60,014
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Val141=
Coding: c.423G>T
MANE Select: NM_000304
dbSNP: rs144077495
Type: single nucleotide variant
Location: chr17:15230977 (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

Similar variants

PMP22 p.Val141Met Uncertain significance ★ ⚠ same residue
PMP22 p.Val141Gly 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
PMP22 p.Gly107Val 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/pmp22-p-val141 (accessed [today's date]).

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