Is ARR3 p.Leu80Pro (c.239T>C) pathogenic?

ARR3 p.Leu80Pro (c.239T>C) is classified Pathogenic in ARR3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-12-22). AlphaMissense: ambiguous (0.5425); Absent from gnomAD v4.1; Associated with myopia 26, X-linked, female-limited.

What condition is associated with ARR3 p.Leu80Pro (c.239T>C)?

ARR3 p.Leu80Pro (c.239T>C) is associated with myopia 26, X-linked, female-limited (ClinVar).

How common is ARR3 p.Leu80Pro (c.239T>C) in the general population?

ARR3 p.Leu80Pro (c.239T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARR3 p.Leu80Pro (c.239T>C)?

AlphaMissense predicts ambiguous (score 0.5425) — an in-silico prediction, not a clinical call.

ARR3 p.Leu80Pro

c.239T>C · rs1555941116 · VCV478826

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5425 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

myopia 26, X-linked, female-limited

Computational evidence

Protein change
AlphaMissense	0.5425	ambiguous
REVEL	0.076	moderately benign-leaning
SaProt	LLR -13.11	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 2.4	GERP -2.7, phastCons 0.75
Regional constraint	o/e 0.85	unconstrained · MANE · 12 kb · p 0.01 · regional, not allelic
Overall
CADD	12.33	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARR3
Protein: p.Leu80Pro
Coding: c.239T>C
MANE Select: NM_004312
dbSNP: rs1555941116
Type: single nucleotide variant
Location: chrX:70276175 (GRCh38)
Structure: AlphaFold pLDDT 87.37
Residue 80: 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

myopia 26, X-linked, female-limited — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARR3 p.Leu80= Likely benign ★ same residue
ARR3 c.767+1G>A Pathogenic/Likely pathogenic ★★ same condition
ARR3 p.Arg72Ter Pathogenic/Likely pathogenic ★★ same condition
ARR3 c.1076+1G>A Uncertain significance ★ same condition
ARR3 c.609+5G>C Uncertain significance ★ same condition
ARR3 p.Arg185Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
ARR3 p.Val322Asp Uncertain significance ★ ⚠ same condition
ARR3 p.Ala298Asp Pathogenic 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-leu80pro (accessed [today's date]).

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