Is ASS1 p.Thr119Pro (c.355A>C) pathogenic?

ASS1 p.Thr119Pro (c.355A>C) is classified Uncertain significance in ASS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2014-10-06). AlphaMissense: likely pathogenic (0.9466); Absent from gnomAD v4.1.

How common is ASS1 p.Thr119Pro (c.355A>C) in the general population?

ASS1 p.Thr119Pro (c.355A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASS1 p.Thr119Pro (c.355A>C)?

AlphaMissense predicts likely pathogenic (score 0.9466) — an in-silico prediction, not a clinical call.

ASS1 p.Thr119Pro

c.355A>C · rs794727696 · VCV197622

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9466 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9466	likely pathogenic
REVEL	0.987	strongly pathogenic-leaning
SaProt	LLR -14.02	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 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 49 kb · p 6.7e-05 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Thr119Pro
Coding: c.355A>C
MANE Select: NM_054012
dbSNP: rs794727696
Type: single nucleotide variant
Location: chr9:130458581 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 119: a UniProt-annotated variant site (in ctln1); a UniProt-annotated variant site (in ctln1; decreased thermal stability; loss of argininosuccinate synthase activity); a binding site

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

Similar variants

ASS1 p.Thr119Ile Pathogenic/Likely pathogenic ★★ same residue
ASS1 c.1194-1G>C Pathogenic/Likely pathogenic ★★ same type
ASS1 c.174+1G>A Pathogenic/Likely pathogenic ★★ same type
ASS1 c.174+1G>T Pathogenic/Likely pathogenic ★★ same type
ASS1 c.175-1119G>A Pathogenic/Likely pathogenic ★★ same type
ASS1 c.364-2A>C Pathogenic/Likely pathogenic ★★ same type
ASS1 c.364-2A>G Pathogenic ★★ same type
ASS1 c.364-2A>T Likely pathogenic ★★ same type

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-thr119pro (accessed [today's date]).

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