Is ARR3 p.Arg166Gln (c.497G>A) pathogenic?

ARR3 p.Arg166Gln (c.497G>A) is classified Uncertain significance in ARR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: ambiguous (0.3708); Ultra-rare (popmax 0.0153%, amr); Associated with Inborn genetic diseases.

What condition is associated with ARR3 p.Arg166Gln (c.497G>A)?

ARR3 p.Arg166Gln (c.497G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ARR3 p.Arg166Gln (c.497G>A) in the general population?

ARR3 p.Arg166Gln (c.497G>A) is ultra-rare (popmax 0.0153%, amr) (gnomAD).

What do computational predictors say about ARR3 p.Arg166Gln (c.497G>A)?

AlphaMissense predicts ambiguous (score 0.3708) — an in-silico prediction, not a clinical call.

ARR3 p.Arg166Gln

c.497G>A · rs143092777 · VCV3129832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3708 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0153%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3708	ambiguous
REVEL	0.252	benign-leaning
SaProt	LLR -12.42	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -0.78, phastCons 0.005
Regional constraint	o/e 0.85	unconstrained · MANE · 12 kb · p 0.01 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0153% Admixed American · 7/45,696 alleles

Filtering AF 0.00714% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00507%

Overall 0.00232% 28/1,209,491 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0153%	6,528
African / African-American	0.0105%	9,525
Remaining individualsnot grpmax-eligible	0.00631%	15,853
European (non-Finnish)	0.00134%	74,585

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: ARR3
Protein: p.Arg166Gln
Coding: c.497G>A
MANE Select: NM_004312
dbSNP: rs143092777
Type: single nucleotide variant
Location: chrX:70277417 (GRCh38)
Structure: AlphaFold pLDDT 87.37
Residue 166: a UniProt-annotated variant site (in myp26; uncertain significance)

Full ARR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARR3 p.Val82Met Uncertain significance ★★ ⚠ same condition
ARR3 p.Arg282Gln Likely benign ★★ same condition
ARR3 p.Ala357Ser Uncertain significance ★ ⚠ same condition
ARR3 p.Arg185Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
ARR3 p.Arg185Pro Uncertain significance ★ ⚠ same condition
ARR3 p.Arg186Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
ARR3 p.Arg186His Conflicting classifications of pathogenicity ★ ⚠ same condition
ARR3 p.Arg21Gln Uncertain significance ★ ⚠ same condition

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/arr3-p-arg166gln (accessed [today's date]).

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