Is ACTC1 p.Glu228= (c.684G>A) pathogenic?

ACTC1 p.Glu228= (c.684G>A) is classified Likely benign in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ACTC1 p.Glu228= (c.684G>A)?

ACTC1 p.Glu228= (c.684G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ACTC1 p.Glu228= (c.684G>A) in the general population?

ACTC1 p.Glu228= (c.684G>A) is absent from gnomAD v4.1 (gnomAD).

ACTC1 p.Glu228=

c.684G>A · VCV3483539

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP 1.4, phastCons 1
Overall
CADD	9.741	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACTC1
Protein: p.Glu228=
Coding: c.684G>A
MANE Select: NM_005159
Type: single nucleotide variant
Location: chr15:34792214 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB
Residue 228: an α-helix

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACTC1 c.808+3G>A Uncertain significance ★★ same condition
ACTC1 p.Ala28Val Uncertain significance ★★ ⚠ same condition
ACTC1 p.Arg208Cys Uncertain significance ★★ ⚠ same condition
ACTC1 p.Arg208His Uncertain significance ★★ ⚠ same condition
ACTC1 p.Arg64Lys Uncertain significance ★★ ⚠ same condition
ACTC1 p.Asp159Asn Uncertain significance ★★ ⚠ same condition
ACTC1 p.Asp365Asn Uncertain significance ★★ ⚠ same condition
ACTC1 p.Asp53Val 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-glu228 (accessed [today's date]).

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