Is ACTR3 p.Pro290Ala (c.868C>G) pathogenic?

ACTR3 p.Pro290Ala (c.868C>G) is classified Uncertain significance in ACTR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.1594); Absent from gnomAD v4.1.

How common is ACTR3 p.Pro290Ala (c.868C>G) in the general population?

ACTR3 p.Pro290Ala (c.868C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTR3 p.Pro290Ala (c.868C>G)?

AlphaMissense predicts likely benign (score 0.1594) — an in-silico prediction, not a clinical call.

ACTR3 p.Pro290Ala

c.868C>G · VCV4637161

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1594 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1594	likely benign
REVEL	0.449	indeterminate
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 67 kb · p 2.4e-24 · regional, not allelic
Overall
CADD	24.1	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: ACTR3
Protein: p.Pro290Ala
Coding: c.868C>G
MANE Select: NM_005721
Type: single nucleotide variant
Location: chr2:113951488 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 91.64 · 5 PDB

Full ACTR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTR3 p.Arg79Cys Uncertain significance ★ ⚠ same type
ACTR3 p.Asn260Ser Uncertain significance ★ ⚠ same type
ACTR3 p.Asn411Ser Uncertain significance ★ ⚠ same type
ACTR3 p.Gly3Glu Uncertain significance ★ ⚠ same type
ACTR3 p.His80Arg Uncertain significance ★ ⚠ same type
ACTR3 p.Ile253Ser Uncertain significance ★ ⚠ same type
ACTR3 p.Ile67Val Uncertain significance ★ ⚠ same type
ACTR3 p.Leu339Val 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/actr3-p-pro290ala (accessed [today's date]).

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