Is ADGRA3 p.Ser94Pro (c.280T>C) pathogenic?

ADGRA3 p.Ser94Pro (c.280T>C) is classified Likely benign in ADGRA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-05). AlphaMissense: likely benign (0.2232); Rare (popmax 0.207%, afr).

How common is ADGRA3 p.Ser94Pro (c.280T>C) in the general population?

ADGRA3 p.Ser94Pro (c.280T>C) is rare (popmax 0.207%, afr) (gnomAD).

What do computational predictors say about ADGRA3 p.Ser94Pro (c.280T>C)?

AlphaMissense predicts likely benign (score 0.2232) — an in-silico prediction, not a clinical call.

ADGRA3 p.Ser94Pro

c.280T>C · rs114456992 · VCV1122408

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2232 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.207%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2232	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -8.58	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 80 kb · p 9.9e-07 · regional, not allelic
Overall
CADD	24.5	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 0.207% African / African-American · 155/74,918 alleles

Filtering AF 0.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.17%

Overall 0.0107% 172/1,606,780 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.207%	483
Remaining individualsnot grpmax-eligible	0.0128%	7,783
Admixed American	0.00839%	11,917
European (non-Finnish)	0.00034%	293,836

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.Ser94Pro
Coding: c.280T>C
MANE Select: NM_145290
dbSNP: rs114456992
Type: single nucleotide variant
Location: chr4:22473821 (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.Ser94Tyr Uncertain significance ★ ⚠ same residue
ADGRA3 p.Ser94= 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

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-ser94pro (accessed [today's date]).

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