Is ADGRA2 p.Arg799His (c.2396G>A) pathogenic?

ADGRA2 p.Arg799His (c.2396G>A) is classified Likely benign in ADGRA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: likely benign (0.0606); Very rare (popmax 0.00534%, afr).

How common is ADGRA2 p.Arg799His (c.2396G>A) in the general population?

ADGRA2 p.Arg799His (c.2396G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ADGRA2 p.Arg799His (c.2396G>A)?

AlphaMissense predicts likely benign (score 0.0606) — an in-silico prediction, not a clinical call.

ADGRA2 p.Arg799His

c.2396G>A · VCV3496160

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0606	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.31	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 0.83	GERP -4.7, phastCons 0.007
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.0006 · regional, not allelic
Overall
CADD	3.202	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 0.00534% African / African-American · 4/74,904 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00173% 28/1,613,992 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,726
East Asian	0.00445%	22,449
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.00161%	62,106
Finnishnot grpmax-eligible	0.00156%	64,006

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: ADGRA2
Protein: p.Arg799His
Coding: c.2396G>A
MANE Select: NM_032777
Type: single nucleotide variant
Location: chr8:37839507 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.47

Full ADGRA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRA2 c.1608+5T>C Benign ★★ same type
ADGRA2 p.Ala681Thr Benign ★★ ⚠ same type
ADGRA2 p.Arg671= Benign ★★ same type
ADGRA2 p.Ala1082Ser Uncertain significance ★ ⚠ same type
ADGRA2 p.Ala1094Ser Uncertain significance ★ ⚠ same type
ADGRA2 p.Ala1098Val Uncertain significance ★ ⚠ same type
ADGRA2 p.Ala1102Thr Uncertain significance ★ ⚠ same type
ADGRA2 p.Ala1102Val 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/adgra2-p-arg799his (accessed [today's date]).

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