Is ARG1 p.Pro242Ser (c.724C>T) pathogenic?

ARG1 p.Pro242Ser (c.724C>T) is classified Uncertain significance in ARG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-24). AlphaMissense: ambiguous (0.3679); Very rare (popmax 0.00398%, nfe); Associated with arginase deficiency.

What condition is associated with ARG1 p.Pro242Ser (c.724C>T)?

ARG1 p.Pro242Ser (c.724C>T) is associated with arginase deficiency (ClinVar).

How common is ARG1 p.Pro242Ser (c.724C>T) in the general population?

ARG1 p.Pro242Ser (c.724C>T) is very rare (popmax 0.00398%, nfe) (gnomAD).

How is Argininemia inherited?

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

What do computational predictors say about ARG1 p.Pro242Ser (c.724C>T)?

AlphaMissense predicts ambiguous (score 0.3679) — an in-silico prediction, not a clinical call.

ARG1 p.Pro242Ser

c.724C>T · rs765495464 · VCV2198388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3679 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00398%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

arginase deficiency

Computational evidence

Protein change
AlphaMissense	0.3679	ambiguous
REVEL	0.9	moderately pathogenic-leaning
SaProt	LLR -11.78	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00398% European (non-Finnish) · 47/1,180,006 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.0031% 50/1,614,016 alleles · very rare exomes 49/1,461,826 · genomes 1/152,190 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00398%	25,107
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	60,002

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.Pro242Ser
Coding: c.724C>T
MANE Select: NM_000045
dbSNP: rs765495464
Type: single nucleotide variant
Location: chr6:131583413 (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.Pro242= Likely benign ★ 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-pro242ser (accessed [today's date]).

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