Is ADAT2 p.Ala6Val (c.17C>T) pathogenic?

ADAT2 p.Ala6Val (c.17C>T) is classified Uncertain significance in ADAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-24). AlphaMissense: likely benign (0.0857); Very rare (popmax 0.00549%, sas).

How common is ADAT2 p.Ala6Val (c.17C>T) in the general population?

ADAT2 p.Ala6Val (c.17C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about ADAT2 p.Ala6Val (c.17C>T)?

AlphaMissense predicts likely benign (score 0.0857) — an in-silico prediction, not a clinical call.

ADAT2 p.Ala6Val

c.17C>T · VCV4011261

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0857 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0857	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -7.25	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 -1.1	GERP -1.1
Regional constraint	o/e 0.90	unconstrained · MANE · 22 kb · p 0.11 · regional, not allelic
Overall
CADD	5.706	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 0.00549% South Asian · 5/91,082 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00062% 10/1,613,490 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.000254%	393,343

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: ADAT2
Protein: p.Ala6Val
Coding: c.17C>T
MANE Select: NM_182503
Type: single nucleotide variant
Location: chr6:143450642 (GRCh38)
Gene constraint: LOEUF 1.326 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.25 · 1 PDB

Full ADAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAT2 p.Ala19Thr Uncertain significance ★ ⚠ same type
ADAT2 p.Ala5Val Uncertain significance ★ ⚠ same type
ADAT2 p.Arg115Cys Uncertain significance ★ ⚠ same type
ADAT2 p.Arg130Gln Uncertain significance ★ ⚠ same type
ADAT2 p.Arg184Gln Uncertain significance ★ ⚠ same type
ADAT2 p.Arg184Trp Uncertain significance ★ ⚠ same type
ADAT2 p.Arg70Gln Uncertain significance ★ ⚠ same type
ADAT2 p.Asp78Asn 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/adat2-p-ala6val (accessed [today's date]).

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