Is ARID2 p.Pro1727Arg (c.5180C>G) pathogenic?

ARID2 p.Pro1727Arg (c.5180C>G) is classified Uncertain significance in ARID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). AlphaMissense: ambiguous (0.4392); Absent from gnomAD v4.1.

How common is ARID2 p.Pro1727Arg (c.5180C>G) in the general population?

ARID2 p.Pro1727Arg (c.5180C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARID2 p.Pro1727Arg (c.5180C>G)?

AlphaMissense predicts ambiguous (score 0.4392) — an in-silico prediction, not a clinical call.

ARID2 p.Pro1727Arg

c.5180C>G · rs2136462199 · VCV1700964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4392 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4392	ambiguous
REVEL	0.232	benign-leaning
SaProt	LLR -6.96	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 1,448 bp · p 0.11 · regional, not allelic
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

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: ARID2
Protein: p.Pro1727Arg
Coding: c.5180C>G
MANE Select: NM_152641
dbSNP: rs2136462199
Type: single nucleotide variant
Location: chr12:45893452 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 1727: the 'disordered' region; a UniProt-annotated variant site (in css6)

Full ARID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARID2 p.Arg1272Ter Pathogenic ★★ same type
ARID2 p.Arg1677Ter Pathogenic/Likely pathogenic ★★ same type
ARID2 p.Arg1754Ter Pathogenic ★★ same type
ARID2 p.Arg1769Ter Pathogenic ★★ same type
ARID2 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same type
ARID2 p.Gln920Ter Pathogenic ★★ same type
ARID2 p.Ala1335Glu Uncertain significance ★★ ⚠ same type
ARID2 p.Arg1679Gln 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/arid2-p-pro1727arg (accessed [today's date]).

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