Is ACVR2A p.Gly299Arg (c.895G>C) pathogenic?

ACVR2A p.Gly299Arg (c.895G>C) is classified Uncertain significance in ACVR2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-15). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1.

How common is ACVR2A p.Gly299Arg (c.895G>C) in the general population?

ACVR2A p.Gly299Arg (c.895G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACVR2A p.Gly299Arg (c.895G>C)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

ACVR2A p.Gly299Arg

c.895G>C · rs2467808695 · VCV2618834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic · top 3% in ACVR2A
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -16.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 27 kb · p 6.6e-34 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ACVR2A
Protein: p.Gly299Arg
Coding: c.895G>C
MANE Select: NM_001616
dbSNP: rs2467808695
Type: single nucleotide variant
Location: chr2:147918525 (GRCh38)
Gene constraint: LOEUF 0.222 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.20 · 5 PDB
Residue 299: an α-helix; the protein kinase domain

Full ACVR2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACVR2A c.1347+1G>A Uncertain significance ★ same type
ACVR2A p.Ala157Val Uncertain significance ★ ⚠ same type
ACVR2A p.Ala4Val Uncertain significance ★ ⚠ same type
ACVR2A p.Arg162Gly Uncertain significance ★ ⚠ same type
ACVR2A p.Arg24Gly Uncertain significance ★ ⚠ same type
ACVR2A p.Arg363Gln Uncertain significance ★ ⚠ same type
ACVR2A p.Asn108Ser Uncertain significance ★ ⚠ same type
ACVR2A p.Asn332Thr 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/acvr2a-p-gly299arg (accessed [today's date]).

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