Is ARID4B p.Pro779Ser (c.2335C>T) pathogenic?

ARID4B p.Pro779Ser (c.2335C>T) is classified Uncertain significance in ARID4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely benign (0.1019); Very rare (popmax 0.0011%, sas).

How common is ARID4B p.Pro779Ser (c.2335C>T) in the general population?

ARID4B p.Pro779Ser (c.2335C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ARID4B p.Pro779Ser (c.2335C>T)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

ARID4B p.Pro779Ser

c.2335C>T · VCV3784873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -5.69	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 8.3	GERP 1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 14 kb · p 0.25 · regional, not allelic
Overall
CADD	22.3	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

Grpmax group 0.0011% South Asian · 1/90,646 alleles

Overall 0.000124% 2/1,612,222 alleles · very rare exomes 2/1,460,144 · genomes 0/152,078 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,646
European (non-Finnish)	8.48e-05%	1,179,626

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: ARID4B
Protein: p.Pro779Ser
Coding: c.2335C>T
MANE Select: NM_016374
Type: single nucleotide variant
Location: chr1:235182584 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.28 · 1 PDB
Residue 779: 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-pro779ser (accessed [today's date]).

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