Is ADGRF3 p.Pro892Ala (c.2674C>G) pathogenic?

ADGRF3 p.Pro892Ala (c.2674C>G) is classified Uncertain significance in ADGRF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-31). AlphaMissense: likely benign (0.1139); Absent from gnomAD v4.1.

How common is ADGRF3 p.Pro892Ala (c.2674C>G) in the general population?

ADGRF3 p.Pro892Ala (c.2674C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRF3 p.Pro892Ala (c.2674C>G)?

AlphaMissense predicts likely benign (score 0.1139) — an in-silico prediction, not a clinical call.

ADGRF3 p.Pro892Ala

c.2674C>G · rs775227693 · VCV3085564

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1139 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1139	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -5.69	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 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.0006 · regional, not allelic
Overall
CADD	21.5	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P960A vs ClinVar P892A) — verify the residue.

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: ADGRF3
Protein: p.Pro892Ala
Coding: c.2674C>G
MANE Select: NM_001321971
dbSNP: rs775227693
Type: single nucleotide variant
Location: chr2:26310850 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.07

Full ADGRF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRF3 c.115-1315G>A Uncertain significance ★ ⚠ same type
ADGRF3 c.115-1349C>A Uncertain significance ★ ⚠ same type
ADGRF3 c.115-1360G>A Uncertain significance ★ ⚠ same type
ADGRF3 c.115-1415G>A Uncertain significance ★ ⚠ same type
ADGRF3 c.115-1448A>G Uncertain significance ★ ⚠ same type
ADGRF3 c.115-1453C>T Uncertain significance ★ ⚠ same type
ADGRF3 c.115-1477C>T Uncertain significance ★ ⚠ same type
ADGRF3 c.115-1480G>A 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/adgrf3-p-pro892ala (accessed [today's date]).

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