Is ACTG1 p.Phe200fs (c.598_611del) pathogenic?

ACTG1 p.Phe200fs (c.598611del) is classified Uncertain significance in ACTG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14).

ACTG1 p.Phe200fs

c.598_611del · VCV3731221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -6.7	GERP -3.8
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: ACTG1
Protein: p.Phe200fs
Coding: c.598_611del
MANE Select: NM_001614
Type: Deletion
Location: chr17:81511379 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB

Full ACTG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTG1 p.Phe200Ile Likely pathogenic ★ same residue
ACTG1 p.Phe200= Likely benign ★ same residue
ACTG1 p.Ser235del Uncertain significance ★★ same type
ACTG1 c.985-40del Benign ★★ same type
ACTG1 p.Lys238_Ser239delinsAsn Likely pathogenic ★ same type
ACTG1 c.-6-9del Uncertain significance ★ same type
ACTG1 p.Met123fs Uncertain significance ★ same type
ACTG1 c.803-18del Likely benign ★ 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/actg1-p-phe200fs (accessed [today's date]).

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