Is ASS1 p.Met1Val (c.1A>G) pathogenic?

ASS1 p.Met1Val (c.1A>G) is classified Likely pathogenic in ASS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-01-10). Very rare (popmax 0.000169%, nfe); Associated with citrullinemia type I.

What condition is associated with ASS1 p.Met1Val (c.1A>G)?

ASS1 p.Met1Val (c.1A>G) is associated with citrullinemia type I (ClinVar).

How common is ASS1 p.Met1Val (c.1A>G) in the general population?

ASS1 p.Met1Val (c.1A>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is Citrullinemia type I inherited?

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

ASS1 p.Met1Val

c.1A>G · rs750780742 · VCV550341

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

citrullinemia type I

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.731	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Overall
CADD	18.19	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 0.000169% European (non-Finnish) · 2/1,179,970 alleles

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

Overall 0.000137% 2/1,461,792 alleles · very 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: ASS1
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_054012
dbSNP: rs750780742
Type: single nucleotide variant
Location: chr9:130452229 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB

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

Disease context

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

For Citrullinemia type I (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ASS1 p.Met1Ile Likely pathogenic same residue
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

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-met1val (accessed [today's date]).

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