Is GDAP1 p.Pro231= (c.693A>T) pathogenic?

GDAP1 p.Pro231= (c.693A>T) is classified Conflicting classifications of pathogenicity in GDAP1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0195%, nfe); Associated with Charcot-Marie-Tooth disease.

How common is GDAP1 p.Pro231= (c.693A>T) in the general population?

GDAP1 p.Pro231= (c.693A>T) is ultra-rare (popmax 0.0195%, nfe) (gnomAD).

GDAP1 p.Pro231=

Q: What condition is associated with GDAP1 p.Pro231= (c.693A>T)?

GDAP1 p.Pro231= (c.693A>T) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 4A, Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive (ClinVar).

c.693A>T · rs181157785 · VCV379724

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0195%, nfe)

Conditions

Charcot-Marie-Tooth disease

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 2.1	GERP -3.8, phastCons 1
Overall
CADD	14.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0195% European (non-Finnish) · 176/904,836 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0161%

Overall 0.0138% 181/1,312,646 alleles · ultra-rare exomes 168/1,160,500 · genomes 13/152,146 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0195%	5,141
Remaining individualsnot grpmax-eligible	0.00571%	17,513
Admixed American	0.00336%	29,802

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: GDAP1
Protein: p.Pro231=
Coding: c.693A>T
MANE Select: NM_018972
dbSNP: rs181157785
Type: single nucleotide variant
Location: chr8:74363052 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 231: the gst c-terminal domain

Full GDAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: Charcot-Marie-Tooth disease type 4A Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive Charcot-Marie-Tooth disease recessive intermediate A

Similar variants

GDAP1 p.Pro231Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
GDAP1 p.Pro231Ser Uncertain significance ★ ⚠ same residue
GDAP1 c.311-1G>A Pathogenic/Likely pathogenic ★★ same condition
GDAP1 c.579+1G>A Pathogenic ★★ same condition
GDAP1 c.694+1G>A Pathogenic/Likely pathogenic ★★ same condition
GDAP1 p.Arg120Trp Pathogenic ★★ ⚠ same condition
GDAP1 p.Arg125Ter Pathogenic ★★ same condition
GDAP1 p.Arg161His 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/gdap1-p-pro231 (accessed [today's date]).

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