Is ARID2 p.Arg274Ter (c.820C>T) pathogenic?

ARID2 p.Arg274Ter (c.820C>T) is classified Pathogenic/Likely pathogenic in ARID2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-10). Absent from gnomAD v4.1; Associated with ARID2-related BAFopathy.

What condition is associated with ARID2 p.Arg274Ter (c.820C>T)?

ARID2 p.Arg274Ter (c.820C>T) is associated with ARID2-related BAFopathy, Coffin-Siris syndrome 6 (ClinVar).

How common is ARID2 p.Arg274Ter (c.820C>T) in the general population?

ARID2 p.Arg274Ter (c.820C>T) is absent from gnomAD v4.1 (gnomAD).

ARID2 p.Arg274Ter

c.820C>T · rs1943228378 · VCV1031208

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,012)

Conditions

ARID2-related BAFopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 21
Splicing
SpliceAI	Δ0.20	donor loss, 35 bp away · masked 0 · deltas
Pangolin	Δ0.21	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Overall
CADD	46.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,012). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARID2
Protein: p.Arg274Ter
Coding: c.820C>T
MANE Select: NM_152641
dbSNP: rs1943228378
Type: single nucleotide variant
Location: chr12:45836788 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB

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

Disease context

ARID2-related BAFopathy

Also linked: Coffin-Siris syndrome 6

Similar variants

ARID2 p.Arg1272Ter Pathogenic ★★ same condition
ARID2 p.Arg1677Ter Pathogenic/Likely pathogenic ★★ same condition
ARID2 p.Arg1754Ter 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-arg274ter (accessed [today's date]).

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