Is ADAT1 p.Pro496Arg (c.1487C>G) pathogenic?

ADAT1 p.Pro496Arg (c.1487C>G) is classified Uncertain significance in ADAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely benign (0.0843); Very rare (popmax 0.00891%, eas).

How common is ADAT1 p.Pro496Arg (c.1487C>G) in the general population?

ADAT1 p.Pro496Arg (c.1487C>G) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about ADAT1 p.Pro496Arg (c.1487C>G)?

AlphaMissense predicts likely benign (score 0.0843) — an in-silico prediction, not a clinical call.

ADAT1 p.Pro496Arg

c.1487C>G · VCV4011214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0843 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0843	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -6.05	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 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 21 kb · p 8.1e-08 · regional, not allelic
Overall
CADD	14.52	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 0.00891% East Asian · 4/44,898 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000248% 4/1,614,028 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.Pro496Arg
Coding: c.1487C>G
MANE Select: NM_001324445
Type: single nucleotide variant
Location: chr16:75600238 (GRCh38)
Gene constraint: LOEUF 1.193 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.40
Residue 496: the a to i editase domain

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

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-pro496arg (accessed [today's date]).

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