Is ARR3 p.Arg72Ter (c.214C>T) pathogenic?

ARR3 p.Arg72Ter (c.214C>T) is classified Pathogenic/Likely pathogenic in ARR3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-09-28). Very rare (popmax 0.000335%, nfe); Associated with ARR3-related disorder.

What condition is associated with ARR3 p.Arg72Ter (c.214C>T)?

ARR3 p.Arg72Ter (c.214C>T) is associated with ARR3-related disorder, myopia 26, X-linked, female-limited (ClinVar).

How common is ARR3 p.Arg72Ter (c.214C>T) in the general population?

ARR3 p.Arg72Ter (c.214C>T) is very rare (popmax 0.000335%, nfe) (gnomAD).

ARR3 p.Arg72Ter

c.214C>T · rs2147641058 · VCV1697230

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000335%, nfe)

Conditions

ARR3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP 0.36
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000335% European (non-Finnish) · 3/895,461 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000273% 3/1,098,141 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.Arg72Ter
Coding: c.214C>T
MANE Select: NM_004312
dbSNP: rs2147641058
Type: single nucleotide variant
Location: chrX:70276150 (GRCh38)
Structure: AlphaFold pLDDT 87.37

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

Disease context

ARR3-related disorder

Also linked: myopia 26, X-linked, female-limited

Similar variants

ARR3 c.767+1G>A Pathogenic/Likely pathogenic ★★ same condition
ARR3 c.8+1G>T Likely pathogenic ★ same condition
ARR3 c.905+2T>G 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-arg72ter (accessed [today's date]).

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