Is ADARB2 p.Val407Met (c.1219G>A) pathogenic?

ADARB2 p.Val407Met (c.1219G>A) is classified Uncertain significance in ADARB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: ambiguous (0.3604); Ultra-rare (popmax 0.0175%, nfe).

How common is ADARB2 p.Val407Met (c.1219G>A) in the general population?

ADARB2 p.Val407Met (c.1219G>A) is ultra-rare (popmax 0.0175%, nfe) (gnomAD).

What do computational predictors say about ADARB2 p.Val407Met (c.1219G>A)?

AlphaMissense predicts ambiguous (score 0.3604) — an in-silico prediction, not a clinical call.

ADARB2 p.Val407Met

c.1219G>A · rs200534087 · VCV2367514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3604 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3604	ambiguous
REVEL	0.187	benign-leaning
SaProt	LLR -10.42	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -4.1, phastCons 0.25
Regional constraint	o/e 0.99	unconstrained · MANE · 554 kb · p 0.84 · regional, not allelic
Overall
CADD	16.74	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

Grpmax group 0.0175% European (non-Finnish) · 203/1,160,558 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0155% 243/1,571,714 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0554%	1,804
European (non-Finnish)grpmax	0.0175%	5,717
Remaining individualsnot grpmax-eligible	0.0164%	6,101
Admixed American	0.00943%	10,609
Finnishnot grpmax-eligible	0.00862%	11,605
African / African-American	0.00404%	24,739
South Asian	0.00116%	86,214

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ADARB2
Protein: p.Val407Met
Coding: c.1219G>A
MANE Select: NM_018702
dbSNP: rs200534087
Type: single nucleotide variant
Location: chr10:1242273 (GRCh38)
Gene constraint: LOEUF 0.681 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.69

Full ADARB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADARB2 p.Val407Leu Uncertain significance ★ ⚠ same residue
ADARB2 p.Arg457His Uncertain significance ★★ ⚠ same type
ADARB2 p.Arg457Ser Uncertain significance ★★ ⚠ same type
ADARB2 p.Ala125= Likely benign ★★ same type
ADARB2 p.Arg328= Benign ★★ same type
ADARB2 p.Arg657Gln Benign ★★ same type
ADARB2 p.Glu300Lys Benign ★★ ⚠ same type
ADARB2 p.Ser463= Benign ★★ 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/adarb2-p-val407met (accessed [today's date]).

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