Is ARPP21 p.Arg249= (c.747G>A) pathogenic?

ARPP21 p.Arg249= (c.747G>A) is classified Likely benign in ARPP21 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). Very rare (popmax 6.2e-05%).

How common is ARPP21 p.Arg249= (c.747G>A) in the general population?

ARPP21 p.Arg249= (c.747G>A) is very rare (popmax 6.2e-05%) (gnomAD).

ARPP21 p.Arg249=

c.747G>A · VCV3316070

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Overall
CADD	13.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,072 alleles · very rare exomes 1/1,461,762 · genomes 0/152,310 · joint denominator

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: ARPP21
Protein: p.Arg249=
Coding: c.747G>A
MANE Select: NM_001385562
Type: single nucleotide variant
Location: chr3:35707034 (GRCh38)
Gene constraint: LOEUF 0.711 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.34
Residue 249: the suz domain; the 'disordered' region

Full ARPP21 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARPP21 p.Pro563Leu Likely pathogenic ★ same type
ARPP21 p.Ala12Thr Uncertain significance ★ ⚠ same type
ARPP21 p.Ala179Thr Uncertain significance ★ ⚠ same type
ARPP21 p.Ala440Thr Uncertain significance ★ ⚠ same type
ARPP21 p.Ala498Val Uncertain significance ★ ⚠ same type
ARPP21 p.Ala708Gly Uncertain significance ★ ⚠ same type
ARPP21 p.Ala712Thr Uncertain significance ★ ⚠ same type
ARPP21 p.Ala829Val 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/arpp21-p-arg249 (accessed [today's date]).

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