Is ASL p.Ter465= (c.1395G>A) pathogenic?

ASL p.Ter465= (c.1395G>A) is classified Conflicting classifications of pathogenicity in ASL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-25). Ultra-rare (popmax 0.0335%, eas); Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Ter465= (c.1395G>A)?

ASL p.Ter465= (c.1395G>A) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Ter465= (c.1395G>A) in the general population?

ASL p.Ter465= (c.1395G>A) is ultra-rare (popmax 0.0335%, eas) (gnomAD).

How is Argininosuccinic aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ASL p.Ter465=

c.1395G>A · rs1339615185 · VCV911866

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, eas)

Conditions

argininosuccinic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.6	GERP 1.9, phastCons 1
Overall
CADD	5.589	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 0.0335% East Asian · 15/44,842 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00103% 15/1,453,222 alleles · ultra-rare

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: ASL
Protein: p.Ter465=
Coding: c.1395G>A
MANE Select: NM_000048
dbSNP: rs1339615185
Type: single nucleotide variant
Location: chr7:66092912 (GRCh38)
Gene constraint: LOEUF 0.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.51 · 2 PDB

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

Disease context

argininosuccinic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Argininosuccinic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

ASL c.1062+5G>C Likely pathogenic ★★ same condition
ASL c.1143+1G>T Pathogenic/Likely pathogenic ★★ same condition
ASL c.13-1G>C Pathogenic/Likely pathogenic ★★ same condition
ASL c.291+1G>T Likely pathogenic ★★ same condition
ASL c.348+1G>A Pathogenic/Likely pathogenic ★★ same condition
ASL c.349-1G>A Likely pathogenic ★★ same condition
ASL c.446+1G>A Pathogenic ★★ same condition
ASL c.446+2T>C 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/asl-p-ter465 (accessed [today's date]).

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