Is ARG1 p.Ser5Cys (c.14C>G) pathogenic?

ARG1 p.Ser5Cys (c.14C>G) is classified Uncertain significance in ARG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). AlphaMissense: likely benign (0.1106); Absent from gnomAD v4.1; Associated with arginase deficiency.

What condition is associated with ARG1 p.Ser5Cys (c.14C>G)?

ARG1 p.Ser5Cys (c.14C>G) is associated with arginase deficiency (ClinVar).

How common is ARG1 p.Ser5Cys (c.14C>G) in the general population?

ARG1 p.Ser5Cys (c.14C>G) is absent from gnomAD v4.1 (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.Ser5Cys (c.14C>G)?

AlphaMissense predicts likely benign (score 0.1106) — an in-silico prediction, not a clinical call.

ARG1 p.Ser5Cys

c.14C>G · rs2482310430 · VCV1979830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1106 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

arginase deficiency

Computational evidence

Protein change
AlphaMissense	0.1106	likely benign
REVEL	0.337	indeterminate
SaProt	LLR -8.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.45, phastCons 0.27
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARG1
Protein: p.Ser5Cys
Coding: c.14C>G
MANE Select: NM_000045
dbSNP: rs2482310430
Type: single nucleotide variant
Location: chr6:131573296 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.01 · 60 PDB
Residue 5: 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.Ser5= 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-ser5cys (accessed [today's date]).

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