Is ADGRG3 p.Ser331Leu (c.992C>T) pathogenic?

ADGRG3 p.Ser331Leu (c.992C>T) is classified Uncertain significance in ADGRG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.0832); Absent from gnomAD v4.1.

How common is ADGRG3 p.Ser331Leu (c.992C>T) in the general population?

ADGRG3 p.Ser331Leu (c.992C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRG3 p.Ser331Leu (c.992C>T)?

AlphaMissense predicts likely benign (score 0.0832) — an in-silico prediction, not a clinical call.

ADGRG3 p.Ser331Leu

c.992C>T · rs2506608522 · VCV2238303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0832 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0832	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -6.79	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 -0.5	GERP -2.5
Regional constraint	o/e 0.94	unconstrained · MANE · 20 kb · p 0.12 · regional, not allelic
Overall
CADD	7.535	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADGRG3
Protein: p.Ser331Leu
Coding: c.992C>T
MANE Select: NM_170776
dbSNP: rs2506608522
Type: single nucleotide variant
Location: chr16:57684042 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.48 · 3 PDB
Residue 331: a turn

Full ADGRG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRG3 p.Ala253Thr Uncertain significance ★ ⚠ same type
ADGRG3 p.Ala311Val Uncertain significance ★ ⚠ same type
ADGRG3 p.Ala543Ser Uncertain significance ★ ⚠ same type
ADGRG3 p.Ala546Thr Uncertain significance ★ ⚠ same type
ADGRG3 p.Ala9Pro Uncertain significance ★ ⚠ same type
ADGRG3 p.Arg139Gln Uncertain significance ★ ⚠ same type
ADGRG3 p.Arg149His Uncertain significance ★ ⚠ same type
ADGRG3 p.Arg180Cys 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/adgrg3-p-ser331leu (accessed [today's date]).

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