Is ARID4B p.Pro657Ser (c.1969C>T) pathogenic?

ARID4B p.Pro657Ser (c.1969C>T) is classified Uncertain significance in ARID4B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.2152); Absent from gnomAD v4.1.

How common is ARID4B p.Pro657Ser (c.1969C>T) in the general population?

ARID4B p.Pro657Ser (c.1969C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARID4B p.Pro657Ser (c.1969C>T)?

AlphaMissense predicts likely benign (score 0.2152) — an in-silico prediction, not a clinical call.

ARID4B p.Pro657Ser

c.1969C>T · rs2527297001 · VCV2251425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2152 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2152	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -5.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 14 kb · p 0.25 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARID4B
Protein: p.Pro657Ser
Coding: c.1969C>T
MANE Select: NM_016374
dbSNP: rs2527297001
Type: single nucleotide variant
Location: chr1:235194169 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.28 · 1 PDB
Residue 657: the 'disordered' region

Full ARID4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARID4B p.Val807= Benign ★★ same type
ARID4B p.Ala1009Thr Uncertain significance ★ ⚠ same type
ARID4B p.Ala1075Val Uncertain significance ★ ⚠ same type
ARID4B p.Ala1160Thr Uncertain significance ★ ⚠ same type
ARID4B p.Ala1186Thr Uncertain significance ★ ⚠ same type
ARID4B p.Ala709Val Uncertain significance ★ ⚠ same type
ARID4B p.Ala725Ser Uncertain significance ★ ⚠ same type
ARID4B p.Ala78Pro Uncertain significance ★ ⚠ same type

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/arid4b-p-pro657ser (accessed [today's date]).

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