Is ADGRE2 p.Asp66= (c.198C>T) pathogenic?

ADGRE2 p.Asp66= (c.198C>T) is classified Benign in ADGRE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-04). Common (popmax 14.3%, afr) — too common for a highly-penetrant pathogenic allele.

ADGRE2 p.Asp66=

Q: How common is ADGRE2 p.Asp66= (c.198C>T) in the general population?

ADGRE2 p.Asp66= (c.198C>T) is common (popmax 14.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.198C>T · rs78992533 · VCV2018266

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 14.3%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP -20	GERP -3.3
Overall
CADD	0.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.3% African / African-American · 10,708/74,950 alleles

Filtering AF 14.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 14%

Overall 4.12% 66,406/1,613,614 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.3%	7
South Asian	13.4%	7
Admixed American	7.34%	14
Middle Eastern	7.11%	14
Remaining individualsnot grpmax-eligible	4.68%	21
Finnishnot grpmax-eligible	4.58%	22
Ashkenazi Jewishnot grpmax-eligible	4.33%	23
Amishnot grpmax-eligible	3.73%	27
European (non-Finnish)	2.58%	39
East Asian	2.46%	41

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: ADGRE2
Protein: p.Asp66=
Coding: c.198C>T
MANE Select: NM_013447
dbSNP: rs78992533
Type: single nucleotide variant
Location: chr19:14773939 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 3 PDB
Residue 66: the egf-like 1 domain

Full ADGRE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRE2 p.Ala359Gly Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala44Thr Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala554Val Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala555Ser Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala589Thr Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala603Thr Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala656Thr Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala664Gly 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/adgre2-p-asp66 (accessed [today's date]).

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