Is GDAP1 p.Ile86Val (c.256A>G) pathogenic?

GDAP1 p.Ile86Val (c.256A>G) is classified Uncertain significance in GDAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-23). AlphaMissense: likely benign (0.0778); Ultra-rare (popmax 0.0386%, afr); Associated with Inborn genetic diseases.

What condition is associated with GDAP1 p.Ile86Val (c.256A>G)?

GDAP1 p.Ile86Val (c.256A>G) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4A (ClinVar).

How common is GDAP1 p.Ile86Val (c.256A>G) in the general population?

GDAP1 p.Ile86Val (c.256A>G) is ultra-rare (popmax 0.0386%, afr) (gnomAD).

What do computational predictors say about GDAP1 p.Ile86Val (c.256A>G)?

AlphaMissense predicts likely benign (score 0.0778) — an in-silico prediction, not a clinical call.

GDAP1 p.Ile86Val

c.256A>G · rs144037310 · VCV568895

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0778 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0386%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0778	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 14 kb · p 0.0041 · regional, not allelic
Overall
CADD	21.5	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

Grpmax group 0.0386% African / African-American · 29/75,058 alleles

Filtering AF 0.0276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0238%

Overall 0.00186% 30/1,614,140 alleles · ultra-rare exomes 7/1,461,788 · genomes 23/152,352 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0386%	2,588
European (non-Finnish)	8.47e-05%	1,179,956

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.Ile86Val
Coding: c.256A>G
MANE Select: NM_018972
dbSNP: rs144037310
Type: single nucleotide variant
Location: chr8:74351412 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 86: the gst n-terminal domain; a β-strand

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 p.Ile86Lys 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
GDAP1 p.Arg161His Pathogenic/Likely pathogenic ★★ ⚠ same condition
GDAP1 p.Arg191Ter 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-ile86val (accessed [today's date]).

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