Is ACTB p.Thr297fs (c.890_891del) pathogenic?

ACTB p.Thr297fs (c.890891del) is classified Likely pathogenic in ACTB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-08). Absent from gnomAD; Associated with ACTB Haploinsufficiency syndrome.

What condition is associated with ACTB p.Thr297fs (c.890_891del)?

ACTB p.Thr297fs (c.890_891del) is associated with ACTB Haploinsufficiency syndrome (ClinVar).

How common is ACTB p.Thr297fs (c.890_891del) in the general population?

ACTB p.Thr297fs (c.890_891del) is absent from gnomAD (gnomAD).

ACTB p.Thr297fs

c.890_891del · rs1554329182 · VCV432794

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ACTB Haploinsufficiency syndrome

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	predicted	premature termination codon in exon 5 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 0.63, 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.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACTB
Protein: p.Thr297fs
Coding: c.890_891del
MANE Select: NM_001101
dbSNP: rs1554329182
Type: Microsatellite
Location: chr7:5528097 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 297: a β-strand

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

Disease context

ACTB Haploinsufficiency syndrome

Similar variants

ACTB p.Thr297Ile Uncertain significance ★★ ⚠ same residue
ACTB p.Thr297= Likely benign ★ same residue
ACTB p.Arg183Trp Pathogenic ★★ same condition
ACTB p.Arg206Gly Likely pathogenic ★★ same condition
ACTB p.His40Tyr Pathogenic/Likely pathogenic ★★ same condition
ACTB p.Val159Ala Likely pathogenic ★★ same condition
ACTB p.Val209Leu Likely pathogenic ★★ same condition
ACTB p.Val209Met Pathogenic/Likely pathogenic ★★ 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/actb-p-thr297fs (accessed [today's date]).

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