Is ADAT1 p.Ile115Val (c.343A>G) pathogenic?

ADAT1 p.Ile115Val (c.343A>G) is classified Uncertain significance in ADAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0863); Ultra-rare (popmax 0.0165%, mid).

How common is ADAT1 p.Ile115Val (c.343A>G) in the general population?

ADAT1 p.Ile115Val (c.343A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ADAT1 p.Ile115Val (c.343A>G)?

AlphaMissense predicts likely benign (score 0.0863) — an in-silico prediction, not a clinical call.

ADAT1 p.Ile115Val

c.343A>G · VCV4637882

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0863 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0863	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.79, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 21 kb · p 8.1e-08 · regional, not allelic
Overall
CADD	14.91	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00164% 24/1,461,744 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.0165%	6,072
Remaining individualsnot grpmax-eligible	0.0032%	31,248
European (non-Finnish)	0.000509%	196,656

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.Ile115Val
Coding: c.343A>G
MANE Select: NM_001324445
Type: single nucleotide variant
Location: chr16:75617223 (GRCh38)
Gene constraint: LOEUF 1.193 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.40
Residue 115: 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-ile115val (accessed [today's date]).

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