Is ACTN2 p.Ala266fs (c.796del) pathogenic?

ACTN2 p.Ala266fs (c.796del) is classified Likely pathogenic in ACTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-22). Absent from gnomAD.

How common is ACTN2 p.Ala266fs (c.796del) in the general population?

ACTN2 p.Ala266fs (c.796del) is absent from gnomAD (gnomAD).

ACTN2 p.Ala266fs

c.796del · rs2102919122 · VCV1678144

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 9 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1

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: ACTN2
Protein: p.Ala266fs
Coding: c.796del
MANE Select: NM_001103
dbSNP: rs2102919122
Type: Deletion
Location: chr1:236737133 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.88 · 18 PDB

Full ACTN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTN2 p.Ala266Asp Uncertain significance ★ ⚠ same residue
ACTN2 c.242-2_242-1del Uncertain significance ★★ same type
ACTN2 p.Glu853fs Uncertain significance ★★ same type
ACTN2 p.Pro240fs Uncertain significance ★★ same type
ACTN2 c.784-518del Benign ★★ same type
ACTN2 c.448+1115_615+666del Likely pathogenic ★ same type
ACTN2 p.Ala732_Ile742del Likely pathogenic ★ same type
ACTN2 p.Leu554fs 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/actn2-p-ala266fs (accessed [today's date]).

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