Is APTX p.Arg318Cys (c.952C>T) pathogenic?

APTX p.Arg318Cys (c.952C>T) is classified Uncertain significance in APTX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). Ultra-rare (popmax 0.0187%, afr); Associated with Inborn genetic diseases.

What condition is associated with APTX p.Arg318Cys (c.952C>T)?

APTX p.Arg318Cys (c.952C>T) is associated with Inborn genetic diseases (ClinVar).

How common is APTX p.Arg318Cys (c.952C>T) in the general population?

APTX p.Arg318Cys (c.952C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

APTX p.Arg318Cys

c.952C>T · rs373961930 · VCV3128101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.399	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 16 kb · p 0.77 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,978 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00155% 25/1,613,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,356
Remaining individualsnot grpmax-eligible	0.0032%	31,251
South Asian	0.0022%	45,533
Admixed American	0.00167%	60,008
European (non-Finnish)	0.000508%	196,663

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.Arg318Cys
Coding: c.952C>T
MANE Select: NM_001195248
dbSNP: rs373961930
Type: single nucleotide variant
Location: chr9:32973575 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.52 · 11 PDB
Residue 318: an α-helix

Full APTX 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

Similar variants

APTX p.Arg318His Uncertain significance ★★ same residue
APTX p.Arg318Ser Uncertain significance ★ same residue
APTX p.Arg29His Uncertain significance ★★ same condition
APTX p.Arg3Gln Uncertain significance ★★ same condition
APTX p.Asn120Ser Uncertain significance ★★ same condition
APTX p.Glu103Lys Uncertain significance ★★ same condition
APTX p.Glu131Lys Uncertain significance ★★ same condition
APTX p.His320Leu Uncertain significance ★★ 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/aptx-p-arg318cys (accessed [today's date]).

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