Is ASS1 p.Pro385Ala (c.1153C>G) pathogenic?

ASS1 p.Pro385Ala (c.1153C>G) is classified Uncertain significance in ASS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-05). AlphaMissense: likely benign (0.2974); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with ASS1 p.Pro385Ala (c.1153C>G)?

ASS1 p.Pro385Ala (c.1153C>G) is associated with Inborn genetic diseases, citrullinemia (ClinVar).

How common is ASS1 p.Pro385Ala (c.1153C>G) in the general population?

ASS1 p.Pro385Ala (c.1153C>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ASS1 p.Pro385Ala (c.1153C>G)?

AlphaMissense predicts likely benign (score 0.2974) — an in-silico prediction, not a clinical call.

ASS1 p.Pro385Ala

c.1153C>G · rs775691183 · VCV2146456

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2974	likely benign
REVEL	0.742	pathogenic-leaning
SaProt	LLR -8.02	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 49 kb · p 6.7e-05 · regional, not allelic
Overall
CADD	24.3	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 0.005% Admixed American · 3/59,968 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00031% 5/1,613,716 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,989
European (non-Finnish)	0.00017%	589,967

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.Pro385Ala
Coding: c.1153C>G
MANE Select: NM_054012
dbSNP: rs775691183
Type: single nucleotide variant
Location: chr9:130499530 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 385: a UniProt-annotated variant site (in ctln1); an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: citrullinemia

Similar variants

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
ASS1 c.496-2A>G Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.689-2A>C 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-pro385ala (accessed [today's date]).

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