Is ARG2 p.Ser6Arg (c.18C>G) pathogenic?

ARG2 p.Ser6Arg (c.18C>G) is classified Uncertain significance in ARG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). AlphaMissense: likely benign (0.1457); Absent from gnomAD v4.1.

How common is ARG2 p.Ser6Arg (c.18C>G) in the general population?

ARG2 p.Ser6Arg (c.18C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARG2 p.Ser6Arg (c.18C>G)?

AlphaMissense predicts likely benign (score 0.1457) — an in-silico prediction, not a clinical call.

ARG2 p.Ser6Arg

c.18C>G · rs925334489 · VCV2493482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1457 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1457	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -7.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.048	GERP -4.1, phastCons 0.12
Regional constraint	o/e 0.89	unconstrained · MANE · 31 kb · p 0.02 · regional, not allelic
Overall
CADD	10.77	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: ARG2
Protein: p.Ser6Arg
Coding: c.18C>G
MANE Select: NM_001172
dbSNP: rs925334489
Type: single nucleotide variant
Location: chr14:67619995 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.55 · 18 PDB

Full ARG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARG2 p.Ala308= Benign/Likely benign ★★ same type
ARG2 p.Arg4Trp Likely benign ★★ same type
ARG2 p.Gly36= Benign ★★ same type
ARG2 p.Ala106Pro Uncertain significance ★ ⚠ same type
ARG2 p.Ala123Thr Uncertain significance ★ ⚠ same type
ARG2 p.Ala191Ser Uncertain significance ★ ⚠ same type
ARG2 p.Ala31Asp Uncertain significance ★ ⚠ same type
ARG2 p.Arg105Ser Uncertain significance ★ ⚠ same type

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/arg2-p-ser6arg (accessed [today's date]).

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