Is GDAP1 p.His30= (c.90T>C) pathogenic?

GDAP1 p.His30= (c.90T>C) is classified Benign/Likely benign in GDAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-02). Rare (popmax 0.41%, sas); Associated with Charcot-Marie-Tooth disease type 4A.

What condition is associated with GDAP1 p.His30= (c.90T>C)?

GDAP1 p.His30= (c.90T>C) is associated with Charcot-Marie-Tooth disease type 4A, Charcot-Marie-Tooth disease (ClinVar).

How common is GDAP1 p.His30= (c.90T>C) in the general population?

GDAP1 p.His30= (c.90T>C) is rare (popmax 0.41%, sas) (gnomAD).

How is Charcot-Marie-Tooth disease type 4A inherited?

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

GDAP1 p.His30=

c.90T>C · rs555369956 · VCV467775

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.41%, sas)

Conditions

Charcot-Marie-Tooth disease type 4A

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 0.61	GERP -0.41, phastCons 1
Overall
CADD	13.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.41% South Asian · 373/90,982 alleles

Filtering AF 0.376% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.362%

Overall 0.0348% 560/1,609,066 alleles · rare exomes 539/1,456,718 · genomes 21/152,348 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.41%	244
Middle Eastern	0.033%	3,028
Remaining individualsnot grpmax-eligible	0.0144%	6,923
European (non-Finnish)	0.014%	7,124
African / African-American	0.00934%	10,711
Admixed American	0.00666%	15,007

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.His30=
Coding: c.90T>C
MANE Select: NM_018972
dbSNP: rs555369956
Type: single nucleotide variant
Location: chr8:74350551 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 30: the gst n-terminal domain; a β-strand

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

Disease context

Charcot-Marie-Tooth disease type 4A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease

For Charcot-Marie-Tooth disease type 4A (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

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
GDAP1 p.Arg191Ter Pathogenic/Likely pathogenic ★★ same condition
GDAP1 p.Arg257Ter 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-his30 (accessed [today's date]).

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