Is ARID2 p.Arg1677Ter (c.5029C>T) pathogenic?

ARID2 p.Arg1677Ter (c.5029C>T) is classified Pathogenic/Likely pathogenic in ARID2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-17). Very rare (popmax 0.000169%, nfe); Associated with ARID2-related disorder.

What condition is associated with ARID2 p.Arg1677Ter (c.5029C>T)?

ARID2 p.Arg1677Ter (c.5029C>T) is associated with ARID2-related disorder (ClinVar).

How common is ARID2 p.Arg1677Ter (c.5029C>T) in the general population?

ARID2 p.Arg1677Ter (c.5029C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

ARID2 p.Arg1677Ter

c.5029C>T · rs1368075571 · VCV1196352

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

Rare

very rare (popmax 0.000169%, nfe)

Conditions

ARID2-related disorder

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 17 of 21
Splicing
SpliceAI	Δ0.26	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.7	GERP 2, phastCons 1
Overall
CADD	44.0	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

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,008 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,028 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ARID2
Protein: p.Arg1677Ter
Coding: c.5029C>T
MANE Select: NM_152641
dbSNP: rs1368075571
Type: single nucleotide variant
Location: chr12:45891886 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 1677: a UniProt-annotated variant site (in css6)

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

Disease context

ARID2-related disorder

Similar variants

ARID2 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same condition
ARID2 c.1580+1G>A Pathogenic ★ same condition
ARID2 p.Gln1676Ter Pathogenic ★ same condition
ARID2 p.Gln820Ter Pathogenic ★ same condition
ARID2 p.Ile943Ser Likely pathogenic ★ ⚠ same condition
ARID2 p.Ala496Pro Uncertain significance ★ ⚠ same condition
ARID2 p.Ala524Val Uncertain significance ★ ⚠ same condition
ARID2 p.Ala8Ser Uncertain significance ★ ⚠ 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-arg1677ter (accessed [today's date]).

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