Is ASS1 p.Glu162fs (c.484dup) pathogenic?

ASS1 p.Glu162fs (c.484dup) is classified Pathogenic in ASS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-29). Very rare (popmax 0.00133%, afr); Associated with citrullinemia.

What condition is associated with ASS1 p.Glu162fs (c.484dup)?

ASS1 p.Glu162fs (c.484dup) is associated with citrullinemia, citrullinemia type I (ClinVar).

How common is ASS1 p.Glu162fs (c.484dup) in the general population?

ASS1 p.Glu162fs (c.484dup) is very rare (popmax 0.00133%, afr) (gnomAD).

ASS1 p.Glu162fs

c.484dup · rs1313340299 · VCV813409

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

citrullinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Overall
CADD	35.0	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 0.00133% African / African-American · 1/74,932 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,994 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,932
European (non-Finnish)	0.000169%	590,005

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: ASS1
Protein: p.Glu162fs
Coding: c.484dup
MANE Select: NM_054012
dbSNP: rs1313340299
Type: Duplication
Location: chr9:130466786 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 162: an α-helix; a UniProt-annotated variant site (in ctln1)

Full ASS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: citrullinemia type I

Similar variants

ASS1 p.Glu162Ter Likely pathogenic ★ same residue
ASS1 p.Glu162= Likely benign ★ same residue
ASS1 c.1128-6_1188dup Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.1194-19_1197dup Likely pathogenic ★★ same condition
ASS1 p.Asn271fs Pathogenic/Likely pathogenic ★★ same condition
ASS1 p.Gly230fs Pathogenic ★ same condition
ASS1 p.Leu367fs Likely pathogenic ★ same condition
ASS1 p.Trp326fs Likely 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/ass1-p-glu162fs (accessed [today's date]).

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