Is ARID3A p.Pro43Ser (c.127C>T) pathogenic?

ARID3A p.Pro43Ser (c.127C>T) is classified Uncertain significance in ARID3A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.0755); Ultra-rare (popmax 0.0402%, sas).

How common is ARID3A p.Pro43Ser (c.127C>T) in the general population?

ARID3A p.Pro43Ser (c.127C>T) is ultra-rare (popmax 0.0402%, sas) (gnomAD).

What do computational predictors say about ARID3A p.Pro43Ser (c.127C>T)?

AlphaMissense predicts likely benign (score 0.0755) — an in-silico prediction, not a clinical call.

ARID3A p.Pro43Ser

c.127C>T · rs780064122 · VCV2210456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0755 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0402%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0755	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -7.22	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 -0.67
Regional constraint	o/e 1.17	unconstrained · MANE · 3,118 bp · p 0.0027 · regional, not allelic
Overall
CADD	0.271	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 0.0402% South Asian · 34/84,512 alleles

Filtering AF 0.0296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.0156% 241/1,540,972 alleles · ultra-rare exomes 231/1,388,874 · genomes 10/152,098 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0402%	2,486
European (non-Finnish)	0.017%	5,872
Remaining individualsnot grpmax-eligible	0.01%	10,003
Admixed American	0.00775%	12,897
African / African-American	0.00136%	73,440

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.Pro43Ser
Coding: c.127C>T
MANE Select: NM_005224
dbSNP: rs780064122
Type: single nucleotide variant
Location: chr19:929655 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.23 · 2 PDB
Residue 43: 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-pro43ser (accessed [today's date]).

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