Is ASS1 p.Ala258Val (c.773C>T) pathogenic?

ASS1 p.Ala258Val (c.773C>T) is classified Likely pathogenic in ASS1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-25). AlphaMissense: likely pathogenic (0.8691); Ultra-rare (popmax 0.0428%, sas); Associated with ASS1-related disorder.

What condition is associated with ASS1 p.Ala258Val (c.773C>T)?

ASS1 p.Ala258Val (c.773C>T) is associated with ASS1-related disorder, citrullinemia type I, citrullinemia (ClinVar).

How common is ASS1 p.Ala258Val (c.773C>T) in the general population?

ASS1 p.Ala258Val (c.773C>T) is ultra-rare (popmax 0.0428%, sas) (gnomAD).

What do computational predictors say about ASS1 p.Ala258Val (c.773C>T)?

AlphaMissense predicts likely pathogenic (score 0.8691) — an in-silico prediction, not a clinical call.

ASS1 p.Ala258Val

c.773C>T · rs753078725 · VCV554197

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8691 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0428%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ASS1-related disorder

Computational evidence

Protein change
AlphaMissense	0.8691	likely pathogenic ✓ concordant with ClinVar
REVEL	0.717	pathogenic-leaning
SaProt	LLR -12.73	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 6	GERP 0.12, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 49 kb · p 6.7e-05 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.0428% South Asian · 39/91,086 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0284%

Overall 0.00347% 56/1,613,716 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0428%	2,336
Middle Eastern	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0048%	20,824
Admixed American	0.00167%	60,014
Finnishnot grpmax-eligible	0.00156%	64,042
European (non-Finnish)	0.000932%	107,245

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.Ala258Val
Coding: c.773C>T
MANE Select: NM_054012
dbSNP: rs753078725
Type: single nucleotide variant
Location: chr9:130479800 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 258: 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

ASS1-related disorder

Also linked: citrullinemia type I citrullinemia

Similar variants

ASS1 p.Ala258Thr Uncertain significance ★★ ⚠ same residue
ASS1 p.Ala258Glu Uncertain significance ★ ⚠ 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

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-ala258val (accessed [today's date]).

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