Is ASS1 p.Ser80= (c.240C>T) pathogenic?

ASS1 p.Ser80= (c.240C>T) is classified Conflicting classifications of pathogenicity in ASS1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-02-11). Ultra-rare (popmax 0.0507%, afr); Associated with citrullinemia.

What condition is associated with ASS1 p.Ser80= (c.240C>T)?

ASS1 p.Ser80= (c.240C>T) is associated with citrullinemia, citrullinemia type I (ClinVar).

How common is ASS1 p.Ser80= (c.240C>T) in the general population?

ASS1 p.Ser80= (c.240C>T) is ultra-rare (popmax 0.0507%, afr) (gnomAD).

ASS1 p.Ser80=

c.240C>T · rs147910468 · VCV365251

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0507%, afr)

Conditions

citrullinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -2.9
Overall
CADD	5.479	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0507% African / African-American · 38/74,984 alleles

Filtering AF 0.0379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0334%

Overall 0.00428% 69/1,612,290 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0507%	1,973
Remaining individualsnot grpmax-eligible	0.00802%	12,468
South Asian	0.00659%	15,166
East Asian	0.00223%	44,864
Admixed American	0.00167%	60,014
European (non-Finnish)	0.00153%	65,548

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.Ser80=
Coding: c.240C>T
MANE Select: NM_054012
dbSNP: rs147910468
Type: single nucleotide variant
Location: chr9:130458466 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 80: 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 c.1194-1G>C Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.174+1G>A Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.174+1G>T Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.175-1119G>A Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.364-2A>C Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.364-2A>G Pathogenic ★★ same condition
ASS1 c.364-2A>T Likely pathogenic ★★ same condition
ASS1 c.420+1G>T Pathogenic/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-ser80 (accessed [today's date]).

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