Is ARID1B p.Pro2017Ser (c.6049C>T) pathogenic?

ARID1B p.Pro2017Ser (c.6049C>T) is classified Conflicting classifications of pathogenicity in ARID1B (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-03-17). AlphaMissense: likely benign (0.0701); Very rare (popmax 0.00246%, nfe); Associated with Coffin-Siris syndrome 1.

What condition is associated with ARID1B p.Pro2017Ser (c.6049C>T)?

ARID1B p.Pro2017Ser (c.6049C>T) is associated with Coffin-Siris syndrome 1 (ClinVar).

How common is ARID1B p.Pro2017Ser (c.6049C>T) in the general population?

ARID1B p.Pro2017Ser (c.6049C>T) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about ARID1B p.Pro2017Ser (c.6049C>T)?

AlphaMissense predicts likely benign (score 0.0701) — an in-silico prediction, not a clinical call.

ARID1B p.Pro2017Ser

c.6049C>T · rs774509236 · VCV210303

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0701 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Coffin-Siris syndrome 1

Computational evidence

Protein change
AlphaMissense	0.0701	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -0.11, phastCons 0.077
Regional constraint	o/e 0.90	unconstrained · MANE · 3,019 bp · p 0.053 · regional, not allelic
Overall
CADD	16.77	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P1881S vs ClinVar P2017S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,180,036 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00198% 32/1,613,926 alleles · very rare exomes 29/1,461,778 · genomes 3/152,148 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,691
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00156%	63,916
African / African-American	0.00134%	74,900

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: ARID1B
Protein: p.Pro2017Ser
Coding: c.6049C>T
MANE Select: NM_001374828
dbSNP: rs774509236
Type: single nucleotide variant
Location: chr6:157206821 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.16 · 9 PDB

Full ARID1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Coffin-Siris syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARID1B c.1987-29738G>T Pathogenic ★★ same condition
ARID1B c.2248-2A>G Pathogenic/Likely pathogenic ★★ same condition
ARID1B c.3505-2A>G Pathogenic ★★ same condition
ARID1B c.4058+1G>C Pathogenic ★★ same condition
ARID1B c.4383-1G>A Pathogenic ★★ same condition
ARID1B c.4479+1G>T Pathogenic ★★ same condition
ARID1B c.5264-2A>G Pathogenic/Likely pathogenic ★★ same condition
ARID1B p.Arg1198Ter 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/arid1b-p-pro2017ser (accessed [today's date]).

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