Is GDAP1 p.Pro153= (c.459G>A) pathogenic?

GDAP1 p.Pro153= (c.459G>A) is classified Conflicting classifications of pathogenicity in GDAP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-10-02). Rare (popmax 0.167%, afr); Associated with Inborn genetic diseases.

What condition is associated with GDAP1 p.Pro153= (c.459G>A)?

GDAP1 p.Pro153= (c.459G>A) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4A, Charcot-Marie-Tooth disease (ClinVar).

How common is GDAP1 p.Pro153= (c.459G>A) in the general population?

GDAP1 p.Pro153= (c.459G>A) is rare (popmax 0.167%, afr) (gnomAD).

GDAP1 p.Pro153=

c.459G>A · rs149804782 · VCV467762

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.167%, afr)

Conditions

Inborn genetic diseases

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 0.43	GERP -4.3, phastCons 0.83
Overall
CADD	8.027	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.167% African / African-American · 125/74,984 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.0142% 229/1,613,890 alleles · rare exomes 150/1,461,700 · genomes 79/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.167%	600
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,250
Admixed American	0.015%	6,668
European (non-Finnish)	0.00712%	14,046

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.Pro153=
Coding: c.459G>A
MANE Select: NM_018972
dbSNP: rs149804782
Type: single nucleotide variant
Location: chr8:74360285 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 153: the gst c-terminal domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 4A Charcot-Marie-Tooth disease

Similar variants

GDAP1 p.Pro153Leu Pathogenic/Likely pathogenic ★★ same residue
GDAP1 p.Pro153Ser Likely pathogenic ★ same residue
GDAP1 p.Pro153Gln 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

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-pro153 (accessed [today's date]).

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