Is ACTC1 p.Thr105fs (c.312del) pathogenic?

ACTC1 p.Thr105fs (c.312del) is classified Conflicting classifications of pathogenicity in ACTC1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-08-15). Absent from gnomAD; Associated with atrial septal defect 5.

What condition is associated with ACTC1 p.Thr105fs (c.312del)?

ACTC1 p.Thr105fs (c.312del) is associated with atrial septal defect 5, hypertrophic cardiomyopathy 11, dilated cardiomyopathy 1R (ClinVar).

How common is ACTC1 p.Thr105fs (c.312del) in the general population?

ACTC1 p.Thr105fs (c.312del) is absent from gnomAD (gnomAD).

ACTC1 p.Thr105fs

c.312del · rs1891747424 · VCV846360

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

atrial septal defect 5

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 3 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, 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: ACTC1
Protein: p.Thr105fs
Coding: c.312del
MANE Select: NM_005159
dbSNP: rs1891747424
Type: Deletion
Location: chr15:34793387 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB
Residue 105: a β-strand

Full ACTC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

atrial septal defect 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 11 dilated cardiomyopathy 1R

Similar variants

ACTC1 p.Thr105Ile Uncertain significance ★ ⚠ same residue
ACTC1 p.Asp186fs Uncertain significance ★★ same condition
ACTC1 c.991-10_991-8del Likely benign ★★ same condition
ACTC1 c.119_129+14del Uncertain significance ★ same condition
ACTC1 c.616+4_616+7del Uncertain significance ★ same condition
ACTC1 c.991-2del Uncertain significance ★ same condition
ACTC1 p.Gly148fs Uncertain significance ★ same condition
ACTC1 p.Gly345fs 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/actc1-p-thr105fs (accessed [today's date]).

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