Is ARG1 p.Asp181= (c.543C>T) pathogenic?

ARG1 p.Asp181= (c.543C>T) is classified Likely benign in ARG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-02). Ultra-rare (popmax 0.0329%, mid); Associated with arginase deficiency.

What condition is associated with ARG1 p.Asp181= (c.543C>T)?

ARG1 p.Asp181= (c.543C>T) is associated with arginase deficiency (ClinVar).

How common is ARG1 p.Asp181= (c.543C>T) in the general population?

ARG1 p.Asp181= (c.543C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is Argininemia inherited?

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

ARG1 p.Asp181=

c.543C>T · rs745787043 · VCV517951

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

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
Pangolin	Δ0.20	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -8.1	GERP -4.5
Overall
CADD	3.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000992% 16/1,613,546 alleles · ultra-rare exomes 15/1,461,504 · genomes 1/152,042 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
South Asian	0.00439%	22,769
Admixed American	0.00167%	59,966
Remaining individualsnot grpmax-eligible	0.0016%	62,462
European (non-Finnish)	0.000678%	147,465

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.Asp181=
Coding: c.543C>T
MANE Select: NM_000045
dbSNP: rs745787043
Type: single nucleotide variant
Location: chr6:131582698 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.01 · 60 PDB

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.Asp181fs Likely pathogenic ★ 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
ARG1 c.665+2T>C 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-asp181 (accessed [today's date]).

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