Is ARID2 p.Ser297Phe (c.890C>T) pathogenic?

ARID2 p.Ser297Phe (c.890C>T) is classified Likely pathogenic in ARID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-22). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with Coffin-Siris syndrome 6.

What condition is associated with ARID2 p.Ser297Phe (c.890C>T)?

ARID2 p.Ser297Phe (c.890C>T) is associated with Coffin-Siris syndrome 6 (ClinVar).

How common is ARID2 p.Ser297Phe (c.890C>T) in the general population?

ARID2 p.Ser297Phe (c.890C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARID2 p.Ser297Phe (c.890C>T)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

ARID2 p.Ser297Phe

c.890C>T · rs2138127522 · VCV2584343

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Coffin-Siris syndrome 6

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 1% in ARID2
REVEL	0.619	indeterminate
SaProt	LLR -16.65	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.05	constrained · MANE · 49 bp · p 2.3e-05 · regional, not allelic
Overall
CADD	29.9	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.Ser297Phe
Coding: c.890C>T
MANE Select: NM_152641
dbSNP: rs2138127522
Type: single nucleotide variant
Location: chr12:45836858 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 297: an α-helix

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

Disease context

Coffin-Siris syndrome 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARID2 p.Arg1272Ter Pathogenic ★★ same condition
ARID2 p.Arg1754Ter Pathogenic ★★ same condition
ARID2 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same condition
ARID2 p.Gln920Ter Pathogenic ★★ same condition
ARID2 p.Asn302Ser Uncertain significance ★★ ⚠ same condition
ARID2 p.Glu112Ala Uncertain significance ★★ ⚠ same condition
ARID2 p.Glu1413Gly Uncertain significance ★★ ⚠ same condition
ARID2 p.Ala1434Ser Benign ★★ 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/arid2-p-ser297phe (accessed [today's date]).

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