Is GDAP1 p.Ser37Thr (c.109T>A) pathogenic?

GDAP1 p.Ser37Thr (c.109T>A) is classified Conflicting classifications of pathogenicity in GDAP1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-22). AlphaMissense: likely pathogenic (0.9329); Very rare (popmax 0.000606%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GDAP1 p.Ser37Thr (c.109T>A)?

GDAP1 p.Ser37Thr (c.109T>A) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4A (ClinVar).

How common is GDAP1 p.Ser37Thr (c.109T>A) in the general population?

GDAP1 p.Ser37Thr (c.109T>A) is very rare (popmax 0.000606%, nfe) (gnomAD).

What do computational predictors say about GDAP1 p.Ser37Thr (c.109T>A)?

AlphaMissense predicts likely pathogenic (score 0.9329) — an in-silico prediction, not a clinical call.

GDAP1 p.Ser37Thr

c.109T>A · rs756121249 · VCV426898

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000606%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9329	likely pathogenic
REVEL	0.444	indeterminate
SaProt	LLR -9.77	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 14 kb · p 0.0041 · regional, not allelic
Overall
CADD	29.7	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 0.000606% European (non-Finnish) · 7/1,154,864 alleles

Filtering AF 0.000252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000162%

Overall 0.000441% 7/1,586,524 alleles · very rare exomes 7/1,434,190 · genomes 0/152,334 · 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.Ser37Thr
Coding: c.109T>A
MANE Select: NM_018972
dbSNP: rs756121249
Type: single nucleotide variant
Location: chr8:74350570 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 37: the gst n-terminal domain; an α-helix

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.Ser37= Likely benign ★ 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-ser37thr (accessed [today's date]).

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