Is ACTR8 p.Ile239Phe (c.715A>T) pathogenic?

ACTR8 p.Ile239Phe (c.715A>T) is classified Uncertain significance in ACTR8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: ambiguous (0.4384); Absent from gnomAD v4.1.

How common is ACTR8 p.Ile239Phe (c.715A>T) in the general population?

ACTR8 p.Ile239Phe (c.715A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTR8 p.Ile239Phe (c.715A>T)?

AlphaMissense predicts ambiguous (score 0.4384) — an in-silico prediction, not a clinical call.

ACTR8 p.Ile239Phe

c.715A>T · rs2474693599 · VCV2303507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4384 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4384	ambiguous
REVEL	0.302	indeterminate
SaProt	LLR -7.20	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 13 kb · p 0.0002 · regional, not allelic
Overall
CADD	26.8	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

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: ACTR8
Protein: p.Ile239Phe
Coding: c.715A>T
MANE Select: NM_022899
dbSNP: rs2474693599
Type: single nucleotide variant
Location: chr3:53876683 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30 · 1 PDB

Full ACTR8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTR8 c.406-7T>G Benign ★★ same type
ACTR8 p.Ala171Ser Uncertain significance ★ ⚠ same type
ACTR8 p.Ala270Thr Uncertain significance ★ ⚠ same type
ACTR8 p.Ala388Ser Uncertain significance ★ ⚠ same type
ACTR8 p.Ala427Ser Uncertain significance ★ ⚠ same type
ACTR8 p.Ala436Glu Uncertain significance ★ ⚠ same type
ACTR8 p.Ala483Val Uncertain significance ★ ⚠ same type
ACTR8 p.Ala585Pro 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/actr8-p-ile239phe (accessed [today's date]).

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