Is ADAT1 p.Pro356Ala (c.1066C>G) pathogenic?

ADAT1 p.Pro356Ala (c.1066C>G) is classified Uncertain significance in ADAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). AlphaMissense: ambiguous (0.4217); Very rare (popmax 0.00667%, afr).

How common is ADAT1 p.Pro356Ala (c.1066C>G) in the general population?

ADAT1 p.Pro356Ala (c.1066C>G) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about ADAT1 p.Pro356Ala (c.1066C>G)?

AlphaMissense predicts ambiguous (score 0.4217) — an in-silico prediction, not a clinical call.

ADAT1 p.Pro356Ala

c.1066C>G · VCV3832657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4217 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4217	ambiguous
REVEL	0.714	pathogenic-leaning
SaProt	LLR -10.40	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 21 kb · p 8.1e-08 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,924 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00328% 5/152,212 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.Pro356Ala
Coding: c.1066C>G
MANE Select: NM_001324445
Type: single nucleotide variant
Location: chr16:75608966 (GRCh38)
Gene constraint: LOEUF 1.193 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.40
Residue 356: 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-pro356ala (accessed [today's date]).

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