Is ARG1 p.Phe240= (c.720C>T) pathogenic?

ARG1 p.Phe240= (c.720C>T) is classified Likely benign in ARG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-27). Very rare (popmax 0.00329%, sas); Associated with arginase deficiency.

What condition is associated with ARG1 p.Phe240= (c.720C>T)?

ARG1 p.Phe240= (c.720C>T) is associated with arginase deficiency (ClinVar).

How common is ARG1 p.Phe240= (c.720C>T) in the general population?

ARG1 p.Phe240= (c.720C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

How is Argininemia inherited?

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

ARG1 p.Phe240=

c.720C>T · rs762145115 · VCV1545352

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

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 0.84	GERP -1.4, phastCons 1
Overall
CADD	12.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,078 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000342% 5/1,461,834 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,359
European (non-Finnish)	0.000169%	589,998

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.Phe240=
Coding: c.720C>T
MANE Select: NM_000045
dbSNP: rs762145115
Type: single nucleotide variant
Location: chr6:131583409 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.01 · 60 PDB
Residue 240: a turn

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 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
ARG1 p.Ala125Val 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-phe240 (accessed [today's date]).

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