Is APTX p.Arg247Ter (c.739C>T) pathogenic?

APTX p.Arg247Ter (c.739C>T) is classified Pathogenic/Likely pathogenic in APTX (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-11). Very rare (popmax 0.005%, amr); Associated with APTX-related disorder.

What condition is associated with APTX p.Arg247Ter (c.739C>T)?

APTX p.Arg247Ter (c.739C>T) is associated with APTX-related disorder, epilepsy (ClinVar).

How common is APTX p.Arg247Ter (c.739C>T) in the general population?

APTX p.Arg247Ter (c.739C>T) is very rare (popmax 0.005%, amr) (gnomAD).

APTX p.Arg247Ter

c.739C>T · rs778258042 · VCV2571331

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

APTX-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 8
Splicing
SpliceAI	Δ0.28	donor loss, 31 bp away · masked 0 · deltas
Pangolin	Δ0.20	loss · gain 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.4	GERP -0.14, phastCons 1
Overall
CADD	39.0	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 0.005% Admixed American · 3/59,996 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00155% 25/1,614,064 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,999
East Asian	0.00223%	44,898
European (non-Finnish)	0.00169%	59,002
South Asian	0.0011%	91,080

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: APTX
Protein: p.Arg247Ter
Coding: c.739C>T
MANE Select: NM_001195248
dbSNP: rs778258042
Type: single nucleotide variant
Location: chr9:32984662 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.52 · 11 PDB
Residue 247: the hit domain; an α-helix

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

Disease context

APTX-related disorder

Also linked: epilepsy

Similar variants

APTX p.Arg247Gln Uncertain significance ★★ same residue
APTX p.Trp279Ter Pathogenic ★★ same condition
APTX p.Pro206Leu Pathogenic ★ same condition
APTX c.875-2A>G Pathogenic/Likely pathogenic ★★ same type
APTX p.Ala198Val Likely pathogenic ★★ same type
APTX p.Arg16Ter Pathogenic/Likely pathogenic ★★ same type
APTX p.Gln130Ter Pathogenic/Likely pathogenic ★★ same type
APTX p.Gln187Ter 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/aptx-p-arg247ter (accessed [today's date]).

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