Is ARID1A p.Pro253= (c.759C>G) pathogenic?

ARID1A p.Pro253= (c.759C>G) is classified Benign/Likely benign in ARID1A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). Rare (popmax 0.13%, sas); Associated with intellectual disability, autosomal dominant 14.

What condition is associated with ARID1A p.Pro253= (c.759C>G)?

ARID1A p.Pro253= (c.759C>G) is associated with intellectual disability, autosomal dominant 14 (ClinVar).

How common is ARID1A p.Pro253= (c.759C>G) in the general population?

ARID1A p.Pro253= (c.759C>G) is rare (popmax 0.13%, sas) (gnomAD).

ARID1A p.Pro253=

c.759C>G · rs747694475 · VCV1175604

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.13%, sas)

Conditions

intellectual disability, autosomal dominant 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	GERP 0.29, phastCons 1
Overall
CADD	13.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.13% South Asian · 89/68,464 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.1%

Overall 0.0229% 330/1,440,810 alleles · rare exomes 304/1,288,788 · genomes 26/152,022 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.13%	769
Middle Eastern	0.0926%	1,080
European (non-Finnish)	0.0203%	4,936
Admixed American	0.0182%	5,481
Remaining individualsnot grpmax-eligible	0.0109%	9,161
African / African-American	0.0015%	66,840

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: ARID1A
Protein: p.Pro253=
Coding: c.759C>G
MANE Select: NM_006015
dbSNP: rs747694475
Type: single nucleotide variant
Location: chr1:26697162 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.81 · 7 PDB
Residue 253: the 'disordered' region

Full ARID1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal dominant 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARID1A p.Pro253Ser Likely benign ★★ same residue
ARID1A c.1920+5G>A Likely pathogenic ★★ same condition
ARID1A c.3198+5G>A Likely pathogenic ★★ same condition
ARID1A p.Ala1077Glu Pathogenic/Likely pathogenic ★★ same condition
ARID1A p.Arg1020Lys Likely pathogenic ★★ same condition
ARID1A p.Gln199Ter Likely pathogenic ★★ same condition
ARID1A p.Gln450Ter Pathogenic ★★ same condition
ARID1A p.Gln548Ter 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/arid1a-p-pro253 (accessed [today's date]).

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