Is ACTB p.Ile330fs (c.986dup) pathogenic?

ACTB p.Ile330fs (c.986dup) is classified Likely pathogenic in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). Associated with intellectual disability.

What condition is associated with ACTB p.Ile330fs (c.986dup)?

ACTB p.Ile330fs (c.986dup) is associated with intellectual disability (ClinVar).

ACTB p.Ile330fs

c.986dup · VCV3897588

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

intellectual disability

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3	GERP 0.77, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ACTB
Protein: p.Ile330fs
Coding: c.986dup
MANE Select: NM_001101
Type: Duplication
Location: chr7:5527889 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACTB p.Ile330Val Uncertain significance ★ ⚠ same residue
ACTB p.Ala7Thr Likely pathogenic ★★ same condition
ACTB p.Ser348Leu Pathogenic/Likely pathogenic ★★ same condition
ACTB p.Ala58Val Uncertain significance ★ ⚠ same condition
ACTB p.Leu65Phe Conflicting classifications of pathogenicity ★ ⚠ same condition
ACTB p.Gln246fs Pathogenic ★ same type
ACTB p.Gln360fs Likely pathogenic ★ same type
ACTB p.Ile369fs Likely pathogenic ★ 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/actb-p-ile330fs (accessed [today's date]).

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