Is ADAT3 p.Ala199Val (c.596C>T) pathogenic?

ADAT3 p.Ala199Val (c.596C>T) is classified Uncertain significance in ADAT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). Ultra-rare (popmax 0.0493%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ADAT3 p.Ala199Val (c.596C>T)?

ADAT3 p.Ala199Val (c.596C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADAT3 p.Ala199Val (c.596C>T) in the general population?

ADAT3 p.Ala199Val (c.596C>T) is ultra-rare (popmax 0.0493%, nfe) (gnomAD).

ADAT3 p.Ala199Val

c.596C>T · rs908444236 · VCV2354323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.118	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -2.7, phastCons 0.003
Regional constraint	o/e 1.29	unconstrained · MANE · 1,100 bp · p 7.8e-12 · regional, not allelic
Overall
CADD	8.759	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% European (non-Finnish) · 541/1,098,346 alleles

Filtering AF 0.0458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0445%

Overall 0.0397% 566/1,423,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0493%	2,030
Remaining individualsnot grpmax-eligible	0.022%	4,547
Finnishnot grpmax-eligible	0.0118%	8,440
African / African-American	0.0106%	9,448
Admixed American	0.00326%	30,688

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.Ala199Val
Coding: c.596C>T
MANE Select: NM_138422
dbSNP: rs908444236
Type: single nucleotide variant
Location: chr19:1912643 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.83
Residue 199: the cmp/dcmp-type deaminase domain

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-ala199val (accessed [today's date]).

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