Is GDAP1 p.Val56Ile (c.166G>A) pathogenic?

GDAP1 p.Val56Ile (c.166G>A) is classified Uncertain significance in GDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-05). AlphaMissense: likely benign (0.1781); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 4A.

What condition is associated with GDAP1 p.Val56Ile (c.166G>A)?

GDAP1 p.Val56Ile (c.166G>A) is associated with Charcot-Marie-Tooth disease type 4A (ClinVar).

How common is GDAP1 p.Val56Ile (c.166G>A) in the general population?

GDAP1 p.Val56Ile (c.166G>A) is absent from gnomAD v4.1 (gnomAD).

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

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

What do computational predictors say about GDAP1 p.Val56Ile (c.166G>A)?

AlphaMissense predicts likely benign (score 0.1781) — an in-silico prediction, not a clinical call.

GDAP1 p.Val56Ile

c.166G>A · rs1808860135 · VCV1005685

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1781 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 4A

Computational evidence

Protein change
AlphaMissense	0.1781	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.55	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 14 kb · p 0.0041 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GDAP1
Protein: p.Val56Ile
Coding: c.166G>A
MANE Select: NM_018972
dbSNP: rs1808860135
Type: single nucleotide variant
Location: chr8:74351322 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 56: the gst n-terminal domain

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

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

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

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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-val56ile (accessed [today's date]).

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