Is ARR3 p.Arg185Pro (c.554G>C) pathogenic?

ARR3 p.Arg185Pro (c.554G>C) is classified Uncertain significance in ARR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). AlphaMissense: likely pathogenic (0.5964); Very rare (popmax 0.000112%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ARR3 p.Arg185Pro (c.554G>C)?

ARR3 p.Arg185Pro (c.554G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ARR3 p.Arg185Pro (c.554G>C) in the general population?

ARR3 p.Arg185Pro (c.554G>C) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about ARR3 p.Arg185Pro (c.554G>C)?

AlphaMissense predicts likely pathogenic (score 0.5964) — an in-silico prediction, not a clinical call.

ARR3 p.Arg185Pro

c.554G>C · rs777141143 · VCV2280143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5964 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5964	likely pathogenic
REVEL	0.178	moderately benign-leaning
SaProt	LLR -14.12	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.34	GERP -1.4
Regional constraint	o/e 0.85	unconstrained · MANE · 12 kb · p 0.01 · regional, not allelic
Overall
CADD	18.2	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 0.000112% European (non-Finnish) · 1/895,277 alleles

Overall 9.11e-05% 1/1,097,627 alleles · very rare

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.Arg185Pro
Coding: c.554G>C
MANE Select: NM_004312
dbSNP: rs777141143
Type: single nucleotide variant
Location: chrX:70277474 (GRCh38)
Structure: AlphaFold pLDDT 87.37
Residue 185: 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.Arg185Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
ARR3 p.Val82Met Uncertain significance ★★ ⚠ same condition
ARR3 p.Arg282Gln Likely benign ★★ ⚠ same condition
ARR3 p.Ala357Ser Uncertain significance ★ ⚠ same condition
ARR3 p.Arg166Gln 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-arg185pro (accessed [today's date]).

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