Is ARG1 p.Cys45= (c.135T>C) pathogenic?

ARG1 p.Cys45= (c.135T>C) is classified Likely benign in ARG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-06). Ultra-rare (popmax 0.0107%, afr); Associated with arginase deficiency.

What condition is associated with ARG1 p.Cys45= (c.135T>C)?

ARG1 p.Cys45= (c.135T>C) is associated with arginase deficiency (ClinVar).

How common is ARG1 p.Cys45= (c.135T>C) in the general population?

ARG1 p.Cys45= (c.135T>C) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

How is Argininemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ARG1 p.Cys45=

c.135T>C · rs372415368 · VCV1077974

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

arginase deficiency

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.43	GERP -1.3, phastCons 1
Overall
CADD	8.415	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,932 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00062% 10/1,614,026 alleles · ultra-rare exomes 2/1,461,806 · genomes 8/152,220 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,367
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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: ARG1
Protein: p.Cys45=
Coding: c.135T>C
MANE Select: NM_000045
dbSNP: rs372415368
Type: single nucleotide variant
Location: chr6:131579115 (GRCh38)

Full ARG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arginase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Argininemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Finland)

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/arg1-p-cys45 (accessed [today's date]).

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