Is ADAT3 p.Pro84Arg (c.251C>G) pathogenic?

ADAT3 p.Pro84Arg (c.251C>G) is classified Uncertain significance in ADAT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). Ultra-rare (popmax 0.0312%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ADAT3 p.Pro84Arg (c.251C>G)?

ADAT3 p.Pro84Arg (c.251C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ADAT3 p.Pro84Arg (c.251C>G) in the general population?

ADAT3 p.Pro84Arg (c.251C>G) is ultra-rare (popmax 0.0312%, nfe) (gnomAD).

ADAT3 p.Pro84Arg

c.251C>G · rs746742994 · VCV2336014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.31	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.21, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 1,100 bp · p 7.8e-12 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0312% European (non-Finnish) · 362/1,161,226 alleles

Filtering AF 0.0285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0274%

Overall 0.0243% 380/1,564,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0312%	3,208
Finnishnot grpmax-eligible	0.018%	5,554
Remaining individualsnot grpmax-eligible	0.0116%	8,655
Admixed American	0.00185%	54,058

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: ADAT3
Protein: p.Pro84Arg
Coding: c.251C>G
MANE Select: NM_138422
dbSNP: rs746742994
Type: single nucleotide variant
Location: chr19:1912298 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.83

Full ADAT3 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

ADAT3 p.Leu247Val Uncertain significance ★★ same condition
ADAT3 p.Pro292Leu Uncertain significance ★★ same condition
ADAT3 p.Val223Met Uncertain significance ★★ same condition
ADAT3 p.Asp285Ala Likely benign ★★ same condition
ADAT3 p.Ala105Gly Uncertain significance ★ same condition
ADAT3 p.Ala146Thr Uncertain significance ★ same condition
ADAT3 p.Ala146Val Uncertain significance ★ same condition
ADAT3 p.Ala177Thr Uncertain significance ★ 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/adat3-p-pro84arg (accessed [today's date]).

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