Is GDAP1 p.Lys172Arg (c.515A>G) pathogenic?

GDAP1 p.Lys172Arg (c.515A>G) is classified Uncertain significance in GDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). AlphaMissense: likely benign (0.0818); No allele count reported in gnomAD v4.1 (AN 1,608,524).

How common is GDAP1 p.Lys172Arg (c.515A>G) in the general population?

GDAP1 p.Lys172Arg (c.515A>G) is no allele count reported in gnomAD v4.1 (AN 1,608,524) (gnomAD).

What do computational predictors say about GDAP1 p.Lys172Arg (c.515A>G)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

GDAP1 p.Lys172Arg

c.515A>G · VCV4900872

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,524)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.472	indeterminate
SaProt	LLR -6.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 14 kb · p 0.0041 · regional, not allelic
Overall
CADD	20.6	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

No allele count reported in gnomAD v4.1 (AN 1,608,524). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GDAP1
Protein: p.Lys172Arg
Coding: c.515A>G
MANE Select: NM_018972
Type: single nucleotide variant
Location: chr8:74361914 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 172: the gst c-terminal domain; a cross-link site

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

Similar variants

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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
GDAP1 p.Arg257Ter 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-lys172arg (accessed [today's date]).

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