Is ARID3A p.Pro577Ser (c.1729C>T) pathogenic?

ARID3A p.Pro577Ser (c.1729C>T) is classified Uncertain significance in ARID3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). AlphaMissense: likely benign (0.0628); Very rare (popmax 0.00777%, sas).

How common is ARID3A p.Pro577Ser (c.1729C>T) in the general population?

ARID3A p.Pro577Ser (c.1729C>T) is very rare (popmax 0.00777%, sas) (gnomAD).

What do computational predictors say about ARID3A p.Pro577Ser (c.1729C>T)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

ARID3A p.Pro577Ser

c.1729C>T · VCV3784584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00777%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -5.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.35	donor gain · deltas
Pangolin	Δ0.37	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.15	GERP -2.7, phastCons 0.028
Regional constraint	o/e 0.87	unconstrained · MANE · 7,135 bp · p 0.013 · regional, not allelic
Overall
CADD	10.29	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 0.00777% South Asian · 7/90,136 alleles

Filtering AF 0.00362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00257%

Overall 0.0005% 8/1,598,742 alleles · very rare exomes 8/1,446,556 · genomes 0/152,186 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00777%	12,877
Remaining individualsnot grpmax-eligible	0.00162%	61,732

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: ARID3A
Protein: p.Pro577Ser
Coding: c.1729C>T
MANE Select: NM_005224
Type: single nucleotide variant
Location: chr19:972012 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.23 · 2 PDB
Residue 577: the 'disordered' region

Full ARID3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARID3A c.950+3G>A Benign ★★ same type
ARID3A p.Ala486= Benign ★★ same type
ARID3A p.Glu447= Benign ★★ same type
ARID3A p.Gly551= Benign ★★ same type
ARID3A p.Ser522= Benign/Likely benign ★★ same type
ARID3A p.Ala171Thr Uncertain significance ★ ⚠ same type
ARID3A p.Ala182Val Uncertain significance ★ ⚠ same type
ARID3A p.Ala209Thr 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/arid3a-p-pro577ser (accessed [today's date]).

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