Is ARR3 p.Pro193Ser (c.577C>T) pathogenic?

ARR3 p.Pro193Ser (c.577C>T) is classified Conflicting classifications of pathogenicity in ARR3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-01). AlphaMissense: likely benign (0.158); Rare (popmax 0.274%, mid); Associated with Inborn genetic diseases.

What condition is associated with ARR3 p.Pro193Ser (c.577C>T)?

ARR3 p.Pro193Ser (c.577C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARR3 p.Pro193Ser (c.577C>T) in the general population?

ARR3 p.Pro193Ser (c.577C>T) is rare (popmax 0.274%, mid) (gnomAD).

What do computational predictors say about ARR3 p.Pro193Ser (c.577C>T)?

AlphaMissense predicts likely benign (score 0.158) — an in-silico prediction, not a clinical call.

ARR3 p.Pro193Ser

c.577C>T · rs142364440 · VCV2660807

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.158 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.274%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.158	likely benign
REVEL	0.229	benign-leaning
SaProt	LLR -9.88	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 -0.031	GERP -3.1, phastCons 0.023
Regional constraint	o/e 0.85	unconstrained · MANE · 12 kb · p 0.01 · regional, not allelic
Overall
CADD	21.5	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 0.274% Middle Eastern · 12/4,375 alleles

Filtering AF 0.158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.0189% 229/1,209,790 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.274%	365
Admixed American	0.0895%	1,117
Remaining individualsnot grpmax-eligible	0.0357%	2,799
South Asian	0.0282%	3,540
European (non-Finnish)	0.0155%	6,439
African / African-American	0.00524%	19,078
East Asian	0.00296%	33,762

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.Pro193Ser
Coding: c.577C>T
MANE Select: NM_004312
dbSNP: rs142364440
Type: single nucleotide variant
Location: chrX:70277497 (GRCh38)
Structure: AlphaFold pLDDT 87.37
Residue 193: 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.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
ARR3 p.Arg186His 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-pro193ser (accessed [today's date]).

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