ASS1 p.Val263Glu
c.788T>A · VCV3649201
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9767 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
citrullinemia
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9767 | likely pathogenic ✓ concordant with ClinVar |
|---|---|---|
| REVEL | 0.992 | strongly pathogenic-leaning |
| SaProt | LLR -13.95 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 1.6, phastCons 1 |
| Regional constraint | o/e 0.83 | unconstrained · MANE · 49 kb · p 6.7e-05 · regional, not allelic |
| Overall | ||
| CADD | 29.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ASS1
- Protein
- p.Val263Glu
- Coding
- c.788T>A
- MANE Select
- NM_054012
- Type
- single nucleotide variant
- Location
- chr9:130480399 (GRCh38)
- Gene constraint
- LOEUF 1.14 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.64 · 1 PDB
- Residue 263
- a UniProt-annotated variant site (in ctln1); a UniProt-annotated variant site (in ctln1; mild clinical course; no effect on affinity for aspartate; no effect on affinity for citrulline; decreased argininosuccinate synthase activity)
Similar variants
- ASS1 p.Val263Met Pathogenic ★★ same residue
- ASS1 p.Val263= Likely benign ★ 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>T Likely pathogenic ★★ same condition
- ASS1 c.421-2A>G 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-val263glu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown