Is AADAT p.Asp133Asn (c.397G>A) pathogenic?

AADAT p.Asp133Asn (c.397G>A) is classified Uncertain significance in AADAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: ambiguous (0.5432); Very rare (popmax 6.87e-05%).

How common is AADAT p.Asp133Asn (c.397G>A) in the general population?

AADAT p.Asp133Asn (c.397G>A) is very rare (popmax 6.87e-05%) (gnomAD).

What do computational predictors say about AADAT p.Asp133Asn (c.397G>A)?

AlphaMissense predicts ambiguous (score 0.5432) — an in-silico prediction, not a clinical call.

AADAT p.Asp133Asn

c.397G>A · VCV4635695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5432 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.87e-05%)

Computational evidence

Protein change
AlphaMissense	0.5432	ambiguous
REVEL	0.487	indeterminate
SaProt	LLR -12.20	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 29 kb · p 4.6e-08 · regional, not allelic
Overall
CADD	28.9	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 6.87e-05%

Overall 6.87e-05% 1/1,455,864 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: AADAT
Protein: p.Asp133Asn
Coding: c.397G>A
MANE Select: NM_016228
Type: single nucleotide variant
Location: chr4:170078556 (GRCh38)
Gene constraint: LOEUF 0.625 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 97.42 · 17 PDB

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

Similar variants

AADAT p.Arg212Cys Uncertain significance ★ ⚠ same type
AADAT p.Asn201Ser Uncertain significance ★ ⚠ same type
AADAT p.Cys122Tyr Uncertain significance ★ ⚠ same type
AADAT p.Gln300Arg Uncertain significance ★ ⚠ same type
AADAT p.Glu215Lys Uncertain significance ★ ⚠ same type
AADAT p.Gly153Ser Uncertain significance ★ ⚠ same type
AADAT p.Ile421Val Uncertain significance ★ ⚠ same type
AADAT p.Leu382Phe 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/aadat-p-asp133asn (accessed [today's date]).

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