Is ARR3 p.Pro173Leu (c.518C>T) pathogenic?

ARR3 p.Pro173Leu (c.518C>T) is classified Likely benign in ARR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely benign (0.0542); Very rare (popmax 0.00873%, amr); Associated with Inborn genetic diseases.

What condition is associated with ARR3 p.Pro173Leu (c.518C>T)?

ARR3 p.Pro173Leu (c.518C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARR3 p.Pro173Leu (c.518C>T) in the general population?

ARR3 p.Pro173Leu (c.518C>T) is very rare (popmax 0.00873%, amr) (gnomAD).

What do computational predictors say about ARR3 p.Pro173Leu (c.518C>T)?

AlphaMissense predicts likely benign (score 0.0542) — an in-silico prediction, not a clinical call.

ARR3 p.Pro173Leu

c.518C>T · VCV4585473

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0542 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00873%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0542	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -5.39	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 -0.63	GERP -3.9
Regional constraint	o/e 0.85	unconstrained · MANE · 12 kb · p 0.01 · regional, not allelic
Overall
CADD	3.85	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 0.00873% Admixed American · 4/45,814 alleles

Filtering AF 0.00293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00177%

Overall 0.00182% 22/1,210,078 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00873%	11,453
East Asian	0.00592%	16,879
Finnishnot grpmax-eligible	0.00214%	46,649
Remaining individualsnot grpmax-eligible	0.0021%	47,591
South Asian	0.00176%	56,752
European (non-Finnish)	0.00145%	68,860

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.Pro173Leu
Coding: c.518C>T
MANE Select: NM_004312
Type: single nucleotide variant
Location: chrX:70277438 (GRCh38)
Structure: AlphaFold pLDDT 87.37
Residue 173: 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.Pro173= Likely benign ★ 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.Arg185Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
ARR3 p.Arg185Pro Uncertain significance ★ ⚠ same condition
ARR3 p.Arg186Cys Conflicting classifications of pathogenicity ★ ⚠ 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-pro173leu (accessed [today's date]).

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