Is ARG1 p.Asp158= (c.474T>C) pathogenic?

ARG1 p.Asp158= (c.474T>C) is classified Likely benign in ARG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0773%, afr); Associated with arginase deficiency.

What condition is associated with ARG1 p.Asp158= (c.474T>C)?

ARG1 p.Asp158= (c.474T>C) is associated with arginase deficiency (ClinVar).

How common is ARG1 p.Asp158= (c.474T>C) in the general population?

ARG1 p.Asp158= (c.474T>C) is ultra-rare (popmax 0.0773%, afr) (gnomAD).

How is Argininemia inherited?

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

ARG1 p.Asp158=

c.474T>C · rs144403253 · VCV697430

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0773%, afr)

Conditions

arginase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -4.3
Overall
CADD	0.577	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0773% African / African-American · 58/75,046 alleles

Filtering AF 0.0613% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0556%

Overall 0.00428% 69/1,613,572 alleles · ultra-rare exomes 38/1,461,250 · genomes 31/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0773%	1,294
Remaining individualsnot grpmax-eligible	0.0064%	15,619
Admixed American	0.005%	20,003
East Asian	0.00223%	44,872
South Asian	0.0022%	45,535
European (non-Finnish)	8.48e-05%	1,179,508

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.Asp158=
Coding: c.474T>C
MANE Select: NM_000045
dbSNP: rs144403253
Type: single nucleotide variant
Location: chr6:131582629 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.01 · 60 PDB
Residue 158: an α-helix

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)

Similar variants

ARG1 p.Asp158Asn Uncertain significance ★★ ⚠ same residue
ARG1 p.Asp158Gly Uncertain significance ★ ⚠ same residue
ARG1 c.130+1G>A Pathogenic ★★ same condition
ARG1 c.465+1G>A Likely pathogenic ★★ same condition
ARG1 c.466-1G>C Pathogenic ★★ same condition
ARG1 c.466-2A>G Pathogenic/Likely pathogenic ★★ same condition
ARG1 c.560+2T>C Pathogenic ★★ same condition
ARG1 c.57+1G>A 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/arg1-p-asp158 (accessed [today's date]).

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