Is ADGRE5 p.Pro170Ser (c.508C>T) pathogenic?

ADGRE5 p.Pro170Ser (c.508C>T) is classified Uncertain significance in ADGRE5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely benign (0.1214); Ultra-rare (popmax 0.0374%, afr).

How common is ADGRE5 p.Pro170Ser (c.508C>T) in the general population?

ADGRE5 p.Pro170Ser (c.508C>T) is ultra-rare (popmax 0.0374%, afr) (gnomAD).

What do computational predictors say about ADGRE5 p.Pro170Ser (c.508C>T)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

ADGRE5 p.Pro170Ser

c.508C>T · VCV3271133

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0374%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -5.58	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 -0.7
Regional constraint	o/e 0.93	unconstrained · MANE · 1,226 bp · p 0.54 · regional, not allelic
Overall
CADD	9.844	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 0.0374% African / African-American · 28/74,924 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.00186% 30/1,613,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0374%	2,676
European (non-Finnish)	0.000169%	590,019

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.Pro170Ser
Coding: c.508C>T
MANE Select: NM_078481
Type: single nucleotide variant
Location: chr19:14397106 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.39 · 9 PDB
Residue 170: the egf-like 4; calcium-binding domain; a disulfide bond

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

Similar variants

ADGRE5 p.Pro170Leu Uncertain significance ★ ⚠ same residue
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

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-pro170ser (accessed [today's date]).

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