Is ADGRE1 p.Ser470Pro (c.1408T>C) pathogenic?

ADGRE1 p.Ser470Pro (c.1408T>C) is classified Uncertain significance in ADGRE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-03). AlphaMissense: ambiguous (0.4035); Absent from gnomAD v4.1.

How common is ADGRE1 p.Ser470Pro (c.1408T>C) in the general population?

ADGRE1 p.Ser470Pro (c.1408T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRE1 p.Ser470Pro (c.1408T>C)?

AlphaMissense predicts ambiguous (score 0.4035) — an in-silico prediction, not a clinical call.

ADGRE1 p.Ser470Pro

c.1408T>C · VCV3835393

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4035 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4035	ambiguous
REVEL	0.311	indeterminate
SaProt	LLR -12.23	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 52 kb · p 0.11 · regional, not allelic
Overall
CADD	20.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADGRE1
Protein: p.Ser470Pro
Coding: c.1408T>C
MANE Select: NM_001974
Type: single nucleotide variant
Location: chr19:6916356 (GRCh38)
Gene constraint: LOEUF 0.951 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75
Residue 470: the gain-b domain

Full ADGRE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRE1 c.2382-4C>T Benign ★★ same type
ADGRE1 p.Arg2Leu Benign ★★ same type
ADGRE1 p.Pro880Thr Benign ★★ same type
ADGRE1 p.Thr885Met Benign ★★ ⚠ same type
ADGRE1 p.Ala177Val Uncertain significance ★ ⚠ same type
ADGRE1 p.Ala57Val Uncertain significance ★ ⚠ same type
ADGRE1 p.Ala592Val Uncertain significance ★ ⚠ same type
ADGRE1 p.Ala620Val 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/adgre1-p-ser470pro (accessed [today's date]).

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