Is ADGRG7 p.Ala583Ser (c.1747G>T) pathogenic?

ADGRG7 p.Ala583Ser (c.1747G>T) is classified Uncertain significance in ADGRG7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.1177); Ultra-rare (popmax 0.0254%, afr).

How common is ADGRG7 p.Ala583Ser (c.1747G>T) in the general population?

ADGRG7 p.Ala583Ser (c.1747G>T) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about ADGRG7 p.Ala583Ser (c.1747G>T)?

AlphaMissense predicts likely benign (score 0.1177) — an in-silico prediction, not a clinical call.

ADGRG7 p.Ala583Ser

c.1747G>T · VCV4638401

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1177 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1177	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -7.70	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 1.1	GERP -1.5
Regional constraint	o/e 0.99	unconstrained · MANE · 85 kb · p 0.79 · regional, not allelic
Overall
CADD	16.88	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 0.0254% African / African-American · 19/74,774 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00125% 20/1,597,438 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,935
Remaining individualsnot grpmax-eligible	0.00162%	61,918

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: ADGRG7
Protein: p.Ala583Ser
Coding: c.1747G>T
MANE Select: NM_032787
Type: single nucleotide variant
Location: chr3:100655919 (GRCh38)
Gene constraint: LOEUF 1.194 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.48

Full ADGRG7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRG7 p.Ala731Thr Benign/Likely benign ★★ same type
ADGRG7 p.Arg756His Benign ★★ same type
ADGRG7 p.Gln598= Benign ★★ same type
ADGRG7 p.Val11= Benign ★★ same type
ADGRG7 p.Ala112Val Uncertain significance ★ ⚠ same type
ADGRG7 p.Ala443Thr Uncertain significance ★ ⚠ same type
ADGRG7 p.Ala450Thr Uncertain significance ★ ⚠ same type
ADGRG7 p.Ala545Ser 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/adgrg7-p-ala583ser (accessed [today's date]).

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