Is ARID3C p.Arg63Gln (c.188G>A) pathogenic?

ARID3C p.Arg63Gln (c.188G>A) is classified Uncertain significance in ARID3C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-09). AlphaMissense: likely benign (0.0621); Very rare (popmax 0.00223%, eas).

How common is ARID3C p.Arg63Gln (c.188G>A) in the general population?

ARID3C p.Arg63Gln (c.188G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ARID3C p.Arg63Gln (c.188G>A)?

AlphaMissense predicts likely benign (score 0.0621) — an in-silico prediction, not a clinical call.

ARID3C p.Arg63Gln

c.188G>A · rs769766423 · VCV2325053

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0621 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0621	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.10	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 -0.16	GERP -3.4
Regional constraint	o/e 1.06	unconstrained · MANE · 6,553 bp · p 0.17 · regional, not allelic
Overall
CADD	12.43	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 0.00223% East Asian · 1/44,820 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000869% 14/1,611,630 alleles · very rare exomes 13/1,459,408 · genomes 1/152,222 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,182
East Asiangrpmax	0.00223%	44,820
South Asian	0.0011%	90,762
European (non-Finnish)	0.000848%	117,902

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ARID3C
Protein: p.Arg63Gln
Coding: c.188G>A
MANE Select: NM_001017363
dbSNP: rs769766423
Type: single nucleotide variant
Location: chr9:34627827 (GRCh38)
Gene constraint: LOEUF 1.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.29
Residue 63: the 'disordered' region

Full ARID3C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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ARID3C p.Ala258Val Uncertain significance ★ ⚠ same type
ARID3C p.Ala323Val Uncertain significance ★ ⚠ same type
ARID3C p.Ala391Asp Uncertain significance ★ ⚠ same type
ARID3C p.Ala40Asp Uncertain significance ★ ⚠ same type
ARID3C p.Ala56Asp 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/arid3c-p-arg63gln (accessed [today's date]).

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