Is ASNS p.Arg465Ter (c.1393C>T) pathogenic?

ASNS p.Arg465Ter (c.1393C>T) is classified Pathogenic/Likely pathogenic in ASNS (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-11-05). Very rare (popmax 0.00803%, afr); Associated with Inborn genetic diseases.

What condition is associated with ASNS p.Arg465Ter (c.1393C>T)?

ASNS p.Arg465Ter (c.1393C>T) is associated with Inborn genetic diseases, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome (ClinVar).

How common is ASNS p.Arg465Ter (c.1393C>T) in the general population?

ASNS p.Arg465Ter (c.1393C>T) is very rare (popmax 0.00803%, afr) (gnomAD).

ASNS p.Arg465Ter

c.1393C>T · rs373774032 · VCV836319

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00803%, afr)

Conditions

Inborn genetic diseases

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	predicted	premature termination codon in exon 12 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.31, 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 0.00803% African / African-American · 6/74,708 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00106% 17/1,610,944 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00803%	12,451
Remaining individualsnot grpmax-eligible	0.00321%	31,165
East Asian	0.00223%	44,836
Admixed American	0.00169%	59,338
European (non-Finnish)	0.000594%	168,438

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: ASNS
Protein: p.Arg465Ter
Coding: c.1393C>T
MANE Select: NM_001673
dbSNP: rs373774032
Type: single nucleotide variant
Location: chr7:97853143 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 465: the asparagine synthetase domain

Full ASNS 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: congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome

Similar variants

ASNS p.Arg465Gln Uncertain significance ★ ⚠ same residue
ASNS c.1030+1G>A Likely pathogenic ★★ same condition
ASNS c.1138-1G>A Likely pathogenic ★★ same condition
ASNS c.1239-2A>T Likely pathogenic ★★ same condition
ASNS c.1320+1G>C Likely pathogenic ★★ same condition
ASNS c.1320+1G>T Likely pathogenic ★★ same condition
ASNS c.1321-1G>A Likely pathogenic ★★ same condition
ASNS c.1476+1G>A 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/asns-p-arg465ter (accessed [today's date]).

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