Is ARID2 p.Ser631fs (c.1890_1891dup) pathogenic?

ARID2 p.Ser631fs (c.18901891dup) is classified Likely pathogenic in ARID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). Associated with Coffin-Siris syndrome 6.

What condition is associated with ARID2 p.Ser631fs (c.1890_1891dup)?

ARID2 p.Ser631fs (c.1890_1891dup) is associated with Coffin-Siris syndrome 6 (ClinVar).

ARID2 p.Ser631fs

c.1890_1891dup · VCV4292393

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Coffin-Siris syndrome 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 14 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3	GERP -3.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ARID2
Protein: p.Ser631fs
Coding: c.1890_1891dup
MANE Select: NM_152641
Type: Duplication
Location: chr12:45849752 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 631: a modified residue (phosphoserine); a UniProt-annotated variant site (in css6)

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.Gln134fs Pathogenic/Likely pathogenic ★★ same condition
ARID2 p.Ile37fs Likely pathogenic ★★ same condition
ARID2 p.Ala1219fs Pathogenic ★ same condition
ARID2 p.Asp1368fs Pathogenic ★ same condition
ARID2 p.Asp280fs Pathogenic ★ same condition
ARID2 p.Gln1404fs Pathogenic ★ same condition
ARID2 p.Ile1401fs Pathogenic ★ same condition
ARID2 p.Val40fs 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/arid2-p-ser631fs (accessed [today's date]).

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