Is ACTL6B p.Arg97Pro (c.290G>C) pathogenic?

ACTL6B p.Arg97Pro (c.290G>C) is classified Uncertain significance in ACTL6B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.9147); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACTL6B p.Arg97Pro (c.290G>C)?

ACTL6B p.Arg97Pro (c.290G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ACTL6B p.Arg97Pro (c.290G>C) in the general population?

ACTL6B p.Arg97Pro (c.290G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTL6B p.Arg97Pro (c.290G>C)?

AlphaMissense predicts likely pathogenic (score 0.9147) — an in-silico prediction, not a clinical call.

ACTL6B p.Arg97Pro

c.290G>C · VCV4833798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9147 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9147	likely pathogenic
REVEL	0.646	pathogenic-leaning
SaProt	LLR -12.07	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 4.9	GERP 0.2, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 9,273 bp · p 1.9e-09 · regional, not allelic
Overall
CADD	25.7	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: ACTL6B
Protein: p.Arg97Pro
Coding: c.290G>C
MANE Select: NM_016188
Type: single nucleotide variant
Location: chr7:100655098 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.52
Residue 97: a UniProt-annotated variant site (in dee76)

Full ACTL6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACTL6B p.Arg97Ter Likely pathogenic ★★ same residue
ACTL6B p.Ile408Thr Uncertain significance ★★ ⚠ same condition
ACTL6B p.Met201Ile Uncertain significance ★★ ⚠ same condition
ACTL6B p.Pro232Arg Uncertain significance ★★ ⚠ same condition
ACTL6B p.Ala156Thr Uncertain significance ★ ⚠ same condition
ACTL6B p.Ala379Thr Uncertain significance ★ ⚠ same condition
ACTL6B p.Arg227Gln Uncertain significance ★ ⚠ same condition
ACTL6B p.Arg227Trp Uncertain significance ★ ⚠ same condition

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/actl6b-p-arg97pro (accessed [today's date]).

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