Is GDAP1 p.Asp248= (c.744C>T) pathogenic?

GDAP1 p.Asp248= (c.744C>T) is classified Likely benign in GDAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-29). Ultra-rare (popmax 0.0254%, afr); Associated with Inborn genetic diseases.

What condition is associated with GDAP1 p.Asp248= (c.744C>T)?

GDAP1 p.Asp248= (c.744C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4A (ClinVar).

How common is GDAP1 p.Asp248= (c.744C>T) in the general population?

GDAP1 p.Asp248= (c.744C>T) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

GDAP1 p.Asp248=

c.744C>T · rs370099528 · VCV467765

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, 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 -11	GERP -4.5
Overall
CADD	5.103	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0254% African / African-American · 19/74,920 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00607% 98/1,613,736 alleles · ultra-rare exomes 84/1,461,594 · genomes 14/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,943
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.008%	12,495
European (non-Finnish)	0.00602%	16,616
Admixed American	0.00167%	59,994
South Asian	0.0011%	91,076

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.Asp248=
Coding: c.744C>T
MANE Select: NM_018972
dbSNP: rs370099528
Type: single nucleotide variant
Location: chr8:74364034 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 248: the gst c-terminal domain; an α-helix

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

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-asp248 (accessed [today's date]).

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