Is GDAP1 p.Pro179Gln (c.536C>A) pathogenic?

GDAP1 p.Pro179Gln (c.536C>A) is classified Uncertain significance in GDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-02). AlphaMissense: ambiguous (0.516); Absent from gnomAD v4.1.

How common is GDAP1 p.Pro179Gln (c.536C>A) in the general population?

GDAP1 p.Pro179Gln (c.536C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GDAP1 p.Pro179Gln (c.536C>A)?

AlphaMissense predicts ambiguous (score 0.516) — an in-silico prediction, not a clinical call.

GDAP1 p.Pro179Gln

c.536C>A · rs1131691282 · VCV429256

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.516 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.516	ambiguous
REVEL	0.844	moderately pathogenic-leaning
SaProt	LLR -10.14	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 14 kb · p 0.0041 · regional, not allelic
Overall
CADD	27.6	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

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.Pro179Gln
Coding: c.536C>A
MANE Select: NM_018972
dbSNP: rs1131691282
Type: single nucleotide variant
Location: chr8:74361935 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 179: the gst c-terminal domain; an α-helix

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

Similar variants

GDAP1 p.Pro179fs Pathogenic/Likely pathogenic ★★ 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-pro179gln (accessed [today's date]).

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