Is GDAP1 p.Pro13Ser (c.37C>T) pathogenic?

GDAP1 p.Pro13Ser (c.37C>T) is classified Conflicting classifications of pathogenicity in GDAP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-08). AlphaMissense: likely benign (0.0605); Very rare (popmax 8.48e-05%, nfe); Associated with Charcot-Marie-Tooth disease axonal type 2K.

What condition is associated with GDAP1 p.Pro13Ser (c.37C>T)?

GDAP1 p.Pro13Ser (c.37C>T) is associated with Charcot-Marie-Tooth disease axonal type 2K (ClinVar).

How common is GDAP1 p.Pro13Ser (c.37C>T) in the general population?

GDAP1 p.Pro13Ser (c.37C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about GDAP1 p.Pro13Ser (c.37C>T)?

AlphaMissense predicts likely benign (score 0.0605) — an in-silico prediction, not a clinical call.

GDAP1 p.Pro13Ser

Q: How is Autosomal recessive Charcot-Marie-Tooth disease with hoarseness inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.37C>T · rs1240725448 · VCV1303351

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0605 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Charcot-Marie-Tooth disease axonal type 2K

Computational evidence

Protein change
AlphaMissense	0.0605	likely benign
REVEL	0.384	indeterminate
SaProt	LLR -5.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.98	GERP -0.67, phastCons 0.73
Regional constraint	o/e 0.86	unconstrained · MANE · 14 kb · p 0.0041 · regional, not allelic
Overall
CADD	15.66	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 8.48e-05% European (non-Finnish) · 1/1,179,560 alleles

Overall 6.2e-05% 1/1,613,480 alleles · very rare exomes 1/1,461,102 · genomes 0/152,378 · joint denominator

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.Pro13Ser
Coding: c.37C>T
MANE Select: NM_018972
dbSNP: rs1240725448
Type: single nucleotide variant
Location: chr8:74350498 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB

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

Disease context

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

For Autosomal recessive Charcot-Marie-Tooth disease with hoarseness (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GDAP1 p.Pro13= Likely benign ★ 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.Arg282Cys Pathogenic ★★ same condition
GDAP1 p.Arg310Gln 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-pro13ser (accessed [today's date]).

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