Is ADAD2 p.Arg82Trp (c.244C>T) pathogenic?

ADAD2 p.Arg82Trp (c.244C>T) is classified Uncertain significance in ADAD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: likely benign (0.1005); Ultra-rare (popmax 0.0231%, nfe).

How common is ADAD2 p.Arg82Trp (c.244C>T) in the general population?

ADAD2 p.Arg82Trp (c.244C>T) is ultra-rare (popmax 0.0231%, nfe) (gnomAD).

What do computational predictors say about ADAD2 p.Arg82Trp (c.244C>T)?

AlphaMissense predicts likely benign (score 0.1005) — an in-silico prediction, not a clinical call.

ADAD2 p.Arg82Trp

c.244C>T · rs373376587 · VCV3143633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1005 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1005	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.58	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 -3.3
Regional constraint	o/e 1.38	unconstrained · MANE · 5,740 bp · p 1.6e-26 · regional, not allelic
Overall
CADD	5.544	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 0.0231% European (non-Finnish) · 264/1,143,940 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0199%

Overall 0.0178% 273/1,537,758 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0231%	4,333
Remaining individualsnot grpmax-eligible	0.0101%	9,949
Finnishnot grpmax-eligible	0.00191%	52,372
African / African-American	0.00137%	72,776
South Asian	0.0012%	83,654

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: ADAD2
Protein: p.Arg82Trp
Coding: c.244C>T
MANE Select: NM_001145400
dbSNP: rs373376587
Type: single nucleotide variant
Location: chr16:84191474 (GRCh38)
Gene constraint: LOEUF 1.524 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.35

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-arg82trp (accessed [today's date]).

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