Is ADAD2 p.Phe298Leu (c.892T>C) pathogenic?

ADAD2 p.Phe298Leu (c.892T>C) is classified Uncertain significance in ADAD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely pathogenic (0.8996); Absent from gnomAD v4.1.

How common is ADAD2 p.Phe298Leu (c.892T>C) in the general population?

ADAD2 p.Phe298Leu (c.892T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADAD2 p.Phe298Leu (c.892T>C)?

AlphaMissense predicts likely pathogenic (score 0.8996) — an in-silico prediction, not a clinical call.

ADAD2 p.Phe298Leu

c.892T>C · rs2507730167 · VCV3143512

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8996	likely pathogenic · top 5% in ADAD2
REVEL	0.625	indeterminate
SaProt	LLR -4.54	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 5,740 bp · p 1.6e-26 · regional, not allelic
Overall
CADD	25.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADAD2
Protein: p.Phe298Leu
Coding: c.892T>C
MANE Select: NM_001145400
dbSNP: rs2507730167
Type: single nucleotide variant
Location: chr16:84195537 (GRCh38)
Gene constraint: LOEUF 1.524 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.35
Residue 298: the a to i editase domain

Full ADAD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAD2 p.Arg180Gln Likely benign ★★ same type
ADAD2 c.419-254A>G Uncertain significance ★ same type
ADAD2 c.419-262T>C Uncertain significance ★ same type
ADAD2 c.419-274C>T Uncertain significance ★ same type
ADAD2 c.419-334G>A Uncertain significance ★ same type
ADAD2 c.419-334G>T Uncertain significance ★ same type
ADAD2 c.419-376A>C Uncertain significance ★ same type
ADAD2 c.419-409G>A 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/adad2-p-phe298leu (accessed [today's date]).

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