Is GDAP1 p.Lys39Arg (c.116A>G) pathogenic?

GDAP1 p.Lys39Arg (c.116A>G) is classified Likely pathogenic in GDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-13). AlphaMissense: likely benign (0.3322); Very rare (popmax 8.91e-05%, nfe).

How common is GDAP1 p.Lys39Arg (c.116A>G) in the general population?

GDAP1 p.Lys39Arg (c.116A>G) is very rare (popmax 8.91e-05%, nfe) (gnomAD).

What do computational predictors say about GDAP1 p.Lys39Arg (c.116A>G)?

AlphaMissense predicts likely benign (score 0.3322) — an in-silico prediction, not a clinical call.

GDAP1 p.Lys39Arg

c.116A>G · rs1586794308 · VCV804864

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3322 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.91e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3322	likely benign ⚠ discordant with ClinVar
REVEL	0.291	indeterminate
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.50	donor gain · deltas
Pangolin	Δ0.49	loss · gain 0.03 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 11	GERP 1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 14 kb · p 0.0041 · regional, not allelic
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.91e-05% European (non-Finnish) · 1/1,122,364 alleles

Overall 6.45e-05% 1/1,550,978 alleles · very rare exomes 1/1,398,628 · genomes 0/152,350 · joint denominator

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.Lys39Arg
Coding: c.116A>G
MANE Select: NM_018972
dbSNP: rs1586794308
Type: single nucleotide variant
Location: chr8:74350577 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 39: a UniProt-annotated variant site (found in a patient with hereditary motor neuropathy; uncertain significance); the gst n-terminal domain; an α-helix

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

Similar variants

GDAP1 p.Lys39Asn Uncertain significance ★ ⚠ same residue
GDAP1 c.311-1G>A Pathogenic/Likely pathogenic ★★ same type
GDAP1 c.579+1G>A Pathogenic ★★ same type
GDAP1 c.694+1G>A Pathogenic/Likely pathogenic ★★ same type
GDAP1 p.Arg120Trp Pathogenic ★★ ⚠ same type
GDAP1 p.Arg125Ter Pathogenic ★★ same type
GDAP1 p.Arg161His Pathogenic/Likely pathogenic ★★ ⚠ same type
GDAP1 p.Arg191Ter Pathogenic/Likely pathogenic ★★ same type

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-lys39arg (accessed [today's date]).

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