Is GDAP1 p.Arg273Ter (c.817C>T) pathogenic?

GDAP1 p.Arg273Ter (c.817C>T) is classified Conflicting classifications of pathogenicity in GDAP1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-03-04). Very rare (popmax 0.00267%, afr); Associated with GDAP1-related disorder.

What condition is associated with GDAP1 p.Arg273Ter (c.817C>T)?

GDAP1 p.Arg273Ter (c.817C>T) is associated with GDAP1-related disorder, Charcot-Marie-Tooth disease type 4A (ClinVar).

How common is GDAP1 p.Arg273Ter (c.817C>T) in the general population?

GDAP1 p.Arg273Ter (c.817C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

GDAP1 p.Arg273Ter

c.817C>T · rs150989205 · VCV849494

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

GDAP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 1.9, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,864 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00112% 18/1,613,970 alleles · very rare exomes 13/1,461,886 · genomes 5/152,084 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-Americangrpmax	0.00267%	37,432
European (non-Finnish)	0.0011%	90,770

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg273Ter
Coding: c.817C>T
MANE Select: NM_018972
dbSNP: rs150989205
Type: single nucleotide variant
Location: chr8:74364107 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.68 · 8 PDB
Residue 273: the gst c-terminal domain

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

Disease context

GDAP1-related disorder

Also linked: Charcot-Marie-Tooth disease type 4A

Similar variants

GDAP1 p.Arg273Gly Uncertain significance ★★ ⚠ same residue
GDAP1 p.Arg273Gln Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg273ter (accessed [today's date]).

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