Is APTX p.Asn120Ser (c.359A>G) pathogenic?

APTX p.Asn120Ser (c.359A>G) is classified Uncertain significance in APTX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-27). Very rare (popmax 0.00263%, nfe); Associated with Inborn genetic diseases.

What condition is associated with APTX p.Asn120Ser (c.359A>G)?

APTX p.Asn120Ser (c.359A>G) is associated with Inborn genetic diseases (ClinVar).

How common is APTX p.Asn120Ser (c.359A>G) in the general population?

APTX p.Asn120Ser (c.359A>G) is very rare (popmax 0.00263%, nfe) (gnomAD).

APTX p.Asn120Ser

c.359A>G · rs955636981 · VCV1479074

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00263%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.124	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -2
Regional constraint	o/e 1.01	unconstrained · MANE · 16 kb · p 0.77 · regional, not allelic
Overall
CADD	0.008	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00263% European (non-Finnish) · 31/1,180,044 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00211% 34/1,614,096 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)grpmax	0.00263%	38,066
African / African-American	0.00133%	74,930

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: APTX
Protein: p.Asn120Ser
Coding: c.359A>G
MANE Select: NM_001195248
dbSNP: rs955636981
Type: single nucleotide variant
Location: chr9:32987668 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.52 · 11 PDB

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.Arg29His Uncertain significance ★★ same condition
APTX p.Arg3Gln 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
APTX p.Ile124Leu Uncertain significance ★★ same condition
APTX p.Ile17Phe Uncertain significance ★★ same condition
APTX p.Leu164Pro 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-asn120ser (accessed [today's date]).

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