Is ARG1 p.Pro280fs (c.839del) pathogenic?

ARG1 p.Pro280fs (c.839del) is classified Pathogenic in ARG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-10). No gnomAD frequency available for this variant; Associated with arginase deficiency.

What condition is associated with ARG1 p.Pro280fs (c.839del)?

ARG1 p.Pro280fs (c.839del) is associated with arginase deficiency (ClinVar).

How common is ARG1 p.Pro280fs (c.839del) in the general population?

ARG1 p.Pro280fs (c.839del) is no gnomAD frequency available for this variant (gnomAD).

How is Argininemia inherited?

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

ARG1 p.Pro280fs

c.839del · rs2114551140 · VCV1064873

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

arginase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARG1
Protein: p.Pro280fs
Coding: c.839del
MANE Select: NM_000045
dbSNP: rs2114551140
Type: Deletion
Location: chr6:131583776 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.01 · 60 PDB
Residue 280: 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.Pro280Leu Uncertain significance ★ ⚠ same residue
ARG1 p.Pro280= Likely benign ★ same residue
ARG1 p.Gly272fs Pathogenic/Likely pathogenic ★★ same condition
ARG1 p.His228_Leu229insTer Pathogenic/Likely pathogenic ★★ same condition
ARG1 p.Leu216fs Pathogenic ★★ same condition
ARG1 p.Lys313fs Pathogenic/Likely pathogenic ★★ same condition
ARG1 c.131-7_131-2del Uncertain significance ★★ same condition
ARG1 c.131-8_131-2del 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-pro280fs (accessed [today's date]).

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