Is ARID2 p.Phe60= (c.180C>T) pathogenic?

ARID2 p.Phe60= (c.180C>T) is classified Benign/Likely benign in ARID2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-25). Rare (popmax 0.429%, eas); Associated with Coffin-Siris syndrome 6.

What condition is associated with ARID2 p.Phe60= (c.180C>T)?

ARID2 p.Phe60= (c.180C>T) is associated with Coffin-Siris syndrome 6 (ClinVar).

How common is ARID2 p.Phe60= (c.180C>T) in the general population?

ARID2 p.Phe60= (c.180C>T) is rare (popmax 0.429%, eas) (gnomAD).

ARID2 p.Phe60=

c.180C>T · rs200775326 · VCV735102

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.429%, eas)

Conditions

Coffin-Siris syndrome 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 0.69, phastCons 1
Overall
CADD	14.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.429% East Asian · 192/44,740 alleles

Filtering AF 0.379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.36%

Overall 0.0179% 289/1,612,636 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.429%	233
South Asian	0.0648%	1,542
Remaining individualsnot grpmax-eligible	0.0513%	1,950
African / African-American	0.004%	25,002
Admixed American	0.00334%	29,956
European (non-Finnish)	8.48e-05%	1,179,162

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.Phe60=
Coding: c.180C>T
MANE Select: NM_152641
dbSNP: rs200775326
Type: single nucleotide variant
Location: chr12:45730131 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.30 · 2 PDB
Residue 60: the arid domain; 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-phe60 (accessed [today's date]).

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