Is ADGRE5 p.Ala830Val (c.2489C>T) pathogenic?

ADGRE5 p.Ala830Val (c.2489C>T) is classified Uncertain significance in ADGRE5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.1096); Rare (popmax 0.109%, nfe).

How common is ADGRE5 p.Ala830Val (c.2489C>T) in the general population?

ADGRE5 p.Ala830Val (c.2489C>T) is rare (popmax 0.109%, nfe) (gnomAD).

What do computational predictors say about ADGRE5 p.Ala830Val (c.2489C>T)?

AlphaMissense predicts likely benign (score 0.1096) — an in-silico prediction, not a clinical call.

ADGRE5 p.Ala830Val

c.2489C>T · VCV3497480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1096 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.109%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1096	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.52	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 2.3	phastCons 0.011
Regional constraint	o/e 1.11	unconstrained · MANE · 3,587 bp · p 0.034 · regional, not allelic
Overall
CADD	14.85	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 0.109% European (non-Finnish) · 1,286/1,180,024 alleles

Filtering AF 0.104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.088% 1,420/1,613,712 alleles · rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.112%	892
European (non-Finnish)grpmax	0.109%	918
Admixed American	0.0283%	3,530
African / African-American	0.0227%	4,414
Finnishnot grpmax-eligible	0.0203%	4,925
South Asian	0.0187%	5,357

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala830Val
Coding: c.2489C>T
MANE Select: NM_078481
Type: single nucleotide variant
Location: chr19:14408102 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.39 · 9 PDB
Residue 830: the 'disordered' region

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.Ala388Ser Uncertain significance ★ ⚠ same type
ADGRE5 p.Ala39Thr Uncertain significance ★ ⚠ same type
ADGRE5 p.Ala412Pro 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-ala830val (accessed [today's date]).

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