ASS1 p.Arg127=
c.381G>A · rs1338613142 · VCV1650870
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Conditions
1
citrullinemia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.68 | GERP -2.2, phastCons 0.001 |
| Overall | ||
| CADD | 4.38 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,880 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000248%
4/1,613,942 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,440 |
| European (non-Finnish) | 0.000169% | 589,998 |
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.Arg127=
- Coding
- c.381G>A
- MANE Select
- NM_054012
- dbSNP
- rs1338613142
- Type
- single nucleotide variant
- Location
- chr9:130464128 (GRCh38)
- Gene constraint
- LOEUF 1.14 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.64 · 1 PDB
- Residue 127
- a binding site; an α-helix; a UniProt-annotated variant site (in ctln1); a UniProt-annotated variant site (increased thermal stability; loss of argininosuccinate synthase activity); a UniProt-annotated variant site (in ctln1; increased thermal stability; loss of argininosuccinate synthase activity); a UniProt-annotated variant site (in ctln1; severe clinical course; loss of argininosuccinate synthase activity)
Similar variants
- ASS1 p.Arg127Gln Pathogenic ★★ same residue
- ASS1 p.Arg127Gly Likely pathogenic ★★ same residue
- ASS1 p.Arg127Leu Pathogenic/Likely pathogenic ★★ same residue
- ASS1 p.Arg127Trp Pathogenic/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
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-arg127 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown