Is ADAT1 p.Pro225Arg (c.674C>G) pathogenic?

ADAT1 p.Pro225Arg (c.674C>G) is classified Uncertain significance in ADAT1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.0796); Very rare (popmax 6.84e-05%); Associated with prostate cancer.

What condition is associated with ADAT1 p.Pro225Arg (c.674C>G)?

ADAT1 p.Pro225Arg (c.674C>G) is associated with prostate cancer (ClinVar).

How common is ADAT1 p.Pro225Arg (c.674C>G) in the general population?

ADAT1 p.Pro225Arg (c.674C>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about ADAT1 p.Pro225Arg (c.674C>G)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

ADAT1 p.Pro225Arg

c.674C>G · rs193920811 · VCV161660

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP -3.3
Regional constraint	o/e 1.22	unconstrained · MANE · 21 kb · p 8.1e-08 · regional, not allelic
Overall
CADD	0.141	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,894 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: ADAT1
Protein: p.Pro225Arg
Coding: c.674C>G
MANE Select: NM_001324445
dbSNP: rs193920811
Type: single nucleotide variant
Location: chr16:75612612 (GRCh38)
Gene constraint: LOEUF 1.193 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.40
Residue 225: the a to i editase domain

Full ADAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

prostate cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADAT1 p.Ala204Thr Uncertain significance ★ ⚠ same type
ADAT1 p.Ala241Gly Uncertain significance ★ ⚠ same type
ADAT1 p.Ala268Pro Uncertain significance ★ ⚠ same type
ADAT1 p.Ala276Ser Uncertain significance ★ ⚠ same type
ADAT1 p.Ala276Val Uncertain significance ★ ⚠ same type
ADAT1 p.Ala344Val Uncertain significance ★ ⚠ same type
ADAT1 p.Ala379Glu Uncertain significance ★ ⚠ same type
ADAT1 p.Ala379Val 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/adat1-p-pro225arg (accessed [today's date]).

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