Is ADGRE5 p.Ala388Ser (c.1162G>T) pathogenic?

ADGRE5 p.Ala388Ser (c.1162G>T) is classified Uncertain significance in ADGRE5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: likely benign (0.2066); Ultra-rare (popmax 0.0151%, afr).

How common is ADGRE5 p.Ala388Ser (c.1162G>T) in the general population?

ADGRE5 p.Ala388Ser (c.1162G>T) is ultra-rare (popmax 0.0151%, afr) (gnomAD).

What do computational predictors say about ADGRE5 p.Ala388Ser (c.1162G>T)?

AlphaMissense predicts likely benign (score 0.2066) — an in-silico prediction, not a clinical call.

ADGRE5 p.Ala388Ser

c.1162G>T · VCV3497639

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2066 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0151%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2066	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -6.79	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 3.7	phastCons 0.81
Regional constraint	o/e 1.02	unconstrained · MANE · 2,993 bp · p 0.81 · regional, not allelic
Overall
CADD	17.18	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 0.0151% African / African-American · 11/72,886 alleles

Filtering AF 0.00837% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00649%

Overall 0.000833% 13/1,559,742 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0151%	6,626
Remaining individualsnot grpmax-eligible	0.00333%	30,070

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: ADGRE5
Protein: p.Ala388Ser
Coding: c.1162G>T
MANE Select: NM_078481
Type: single nucleotide variant
Location: chr19:14401739 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.39 · 9 PDB
Residue 388: the gain-b domain; an α-helix

Full ADGRE5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRE5 c.1183+10G>A Benign ★★ same type
ADGRE5 p.Asn371= Benign ★★ same type
ADGRE5 p.Ile666Met Likely benign ★★ ⚠ same type
ADGRE5 p.Leu635= Benign ★★ same type
ADGRE5 p.Ala379Thr Uncertain significance ★ ⚠ same type
ADGRE5 p.Ala39Thr Uncertain significance ★ ⚠ same type
ADGRE5 p.Ala412Pro Uncertain significance ★ ⚠ same type
ADGRE5 p.Ala534Val 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/adgre5-p-ala388ser (accessed [today's date]).

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