Is ADGRA3 p.Glu60Lys (c.178G>A) pathogenic?

ADGRA3 p.Glu60Lys (c.178G>A) is classified Uncertain significance in ADGRA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-25). AlphaMissense: ambiguous (0.5441); Rare (popmax 0.156%, mid).

How common is ADGRA3 p.Glu60Lys (c.178G>A) in the general population?

ADGRA3 p.Glu60Lys (c.178G>A) is rare (popmax 0.156%, mid) (gnomAD).

What do computational predictors say about ADGRA3 p.Glu60Lys (c.178G>A)?

AlphaMissense predicts ambiguous (score 0.5441) — an in-silico prediction, not a clinical call.

ADGRA3 p.Glu60Lys

c.178G>A · rs770806145 · VCV1462688

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5441 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.156%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5441	ambiguous
REVEL	0.081	moderately benign-leaning
SaProt	LLR -7.58	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 1.1, phastCons 0.99
Regional constraint	o/e 0.79	unconstrained · MANE · 80 kb · p 9.9e-07 · regional, not allelic
Overall
CADD	22.8	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

Grpmax group 0.156% Middle Eastern · 8/5,122 alleles

Filtering AF 0.0777% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0566%

Overall 0.00143% 20/1,399,290 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.156%	640
Admixed American	0.00937%	10,672
Remaining individualsnot grpmax-eligible	0.00843%	11,869
Ashkenazi Jewishnot grpmax-eligible	0.0036%	27,740
European (non-Finnish)	8.7e-05%	1,149,600

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: ADGRA3
Protein: p.Glu60Lys
Coding: c.178G>A
MANE Select: NM_145290
dbSNP: rs770806145
Type: single nucleotide variant
Location: chr4:22515607 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20

Full ADGRA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRA3 p.Glu60= Likely benign ★ same residue
ADGRA3 p.Ala1008Val Uncertain significance ★★ ⚠ same type
ADGRA3 p.Ala1120Val Uncertain significance ★★ ⚠ same type
ADGRA3 p.Ala1127Ser Uncertain significance ★★ ⚠ same type
ADGRA3 p.Ala177Val Uncertain significance ★★ ⚠ same type
ADGRA3 p.Ala26Pro Uncertain significance ★★ ⚠ same type
ADGRA3 p.Ala316Pro Uncertain significance ★★ ⚠ same type
ADGRA3 p.Ala37Gly 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/adgra3-p-glu60lys (accessed [today's date]).

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