Is ADGRE2 p.Val77Ala (c.230T>C) pathogenic?

ADGRE2 p.Val77Ala (c.230T>C) is classified Uncertain significance in ADGRE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-08). AlphaMissense: likely benign (0.1706); Very rare (popmax 0.000424%, nfe).

How common is ADGRE2 p.Val77Ala (c.230T>C) in the general population?

ADGRE2 p.Val77Ala (c.230T>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ADGRE2 p.Val77Ala (c.230T>C)?

AlphaMissense predicts likely benign (score 0.1706) — an in-silico prediction, not a clinical call.

ADGRE2 p.Val77Ala

c.230T>C · rs942824515 · VCV3000989

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1706	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -5.81	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 -8.1	GERP -2.9
Regional constraint	o/e 0.89	unconstrained · MANE · 9,655 bp · p 0.17 · regional, not allelic
Overall
CADD	5.081	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 0.000424% European (non-Finnish) · 5/1,180,000 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,730 alleles · very rare

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.Val77Ala
Coding: c.230T>C
MANE Select: NM_013447
dbSNP: rs942824515
Type: single nucleotide variant
Location: chr19:14772467 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 3 PDB
Residue 77: the egf-like 2; calcium-binding domain; a disulfide bond

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-val77ala (accessed [today's date]).

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