Is ADAT1 p.Val193Ile (c.577G>A) pathogenic?

ADAT1 p.Val193Ile (c.577G>A) is classified Uncertain significance in ADAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: likely benign (0.0765); Very rare (popmax 0.00483%, nfe).

How common is ADAT1 p.Val193Ile (c.577G>A) in the general population?

ADAT1 p.Val193Ile (c.577G>A) is very rare (popmax 0.00483%, nfe) (gnomAD).

What do computational predictors say about ADAT1 p.Val193Ile (c.577G>A)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

ADAT1 p.Val193Ile

c.577G>A · rs754541349 · VCV2371380

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00483%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.94	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 -2.9	GERP -3.4
Regional constraint	o/e 1.22	unconstrained · MANE · 21 kb · p 8.1e-08 · regional, not allelic
Overall
CADD	0.451	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 0.00483% European (non-Finnish) · 57/1,180,016 alleles

Filtering AF 0.00377% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00397% 64/1,613,950 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00483%	20,702
Admixed American	0.00333%	29,993
Remaining individualsnot grpmax-eligible	0.0032%	31,240
Finnishnot grpmax-eligible	0.00312%	32,009
African / African-American	0.00134%	74,894

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.Val193Ile
Coding: c.577G>A
MANE Select: NM_001324445
dbSNP: rs754541349
Type: single nucleotide variant
Location: chr16:75612709 (GRCh38)
Gene constraint: LOEUF 1.193 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.40
Residue 193: the a to i editase domain; the 'disordered' region

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-val193ile (accessed [today's date]).

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