Is ARL9 p.Pro247Arg (c.740C>G) pathogenic?

ARL9 p.Pro247Arg (c.740C>G) is classified Uncertain significance in ARL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-11). Very rare (popmax 0.00329%, sas).

How common is ARL9 p.Pro247Arg (c.740C>G) in the general population?

ARL9 p.Pro247Arg (c.740C>G) is very rare (popmax 0.00329%, sas) (gnomAD).

ARL9 p.Pro247Arg

c.740C>G · rs2545805713 · VCV2306545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.138	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 18 kb · p 0.82 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,088 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000205% 3/1,461,682 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: ARL9
Protein: p.Pro247Arg
Coding: c.740C>G
MANE Select: NM_001363794
dbSNP: rs2545805713
Type: single nucleotide variant
Location: chr4:56523818 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.66

Full ARL9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARL9 p.Pro247Leu Uncertain significance ★ same residue
ARL9 p.Ala210Glu Uncertain significance ★ same type
ARL9 p.Ala211Val Uncertain significance ★ same type
ARL9 p.Arg230Lys Uncertain significance ★ same type
ARL9 p.Asn204Asp Uncertain significance ★ same type
ARL9 p.Asn204Lys Uncertain significance ★ same type
ARL9 p.Gln206Glu Uncertain significance ★ same type
ARL9 p.Ile169Met Uncertain significance ★ same type

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/arl9-p-pro247arg (accessed [today's date]).

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