Is PMP22 p.Ser79Pro (c.235T>C) pathogenic?

PMP22 p.Ser79Pro (c.235T>C) is classified Pathogenic in PMP22 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-12-20). AlphaMissense: likely pathogenic (0.9727); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with PMP22 p.Ser79Pro (c.235T>C)?

PMP22 p.Ser79Pro (c.235T>C) is associated with Charcot-Marie-Tooth disease type 1, Charcot-Marie-Tooth disease type 3 (ClinVar).

How common is PMP22 p.Ser79Pro (c.235T>C) in the general population?

PMP22 p.Ser79Pro (c.235T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PMP22 p.Ser79Pro (c.235T>C)?

AlphaMissense predicts likely pathogenic (score 0.9727) — an in-silico prediction, not a clinical call.

PMP22 p.Ser79Pro

c.235T>C · rs863225027 · VCV637822

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9727 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 1

Computational evidence

Protein change
AlphaMissense	0.9727	likely pathogenic ✓ concordant with ClinVar
REVEL	0.878	moderately pathogenic-leaning
SaProt	LLR -15.04	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 6.9	GERP 0.66, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 30 kb · p 0.02 · regional, not allelic
Overall
CADD	24.5	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: PMP22
Protein: p.Ser79Pro
Coding: c.235T>C
MANE Select: NM_000304
dbSNP: rs863225027
Type: single nucleotide variant
Location: chr17:15239555 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 89.87
Residue 79: a UniProt-annotated variant site (in cmt1a); a UniProt-annotated variant site (in dss)

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 type 3

Similar variants

PMP22 p.Ser79Thr Likely pathogenic ★★ same residue
PMP22 p.Ser79Cys Pathogenic ★ same residue
PMP22 p.Ser79Phe Pathogenic ★ 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-ser79pro (accessed [today's date]).

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