Is ACTC1 p.Lys330= (c.990G>A) pathogenic?

ACTC1 p.Lys330= (c.990G>A) is classified Uncertain significance in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). Absent from gnomAD v4.1; Associated with atrial septal defect 5.

What condition is associated with ACTC1 p.Lys330= (c.990G>A)?

ACTC1 p.Lys330= (c.990G>A) is associated with atrial septal defect 5, hypertrophic cardiomyopathy 11, dilated cardiomyopathy 1R (ClinVar).

How common is ACTC1 p.Lys330= (c.990G>A) in the general population?

ACTC1 p.Lys330= (c.990G>A) is absent from gnomAD v4.1 (gnomAD).

ACTC1 p.Lys330=

c.990G>A · rs2504177206 · VCV2922253

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

atrial septal defect 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.73	donor gain · deltas
Pangolin	Δ0.67	loss · gain 0.48 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Overall
CADD	25.5	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.Lys330=
Coding: c.990G>A
MANE Select: NM_005159
dbSNP: rs2504177206
Type: single nucleotide variant
Location: chr15:34791114 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB

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.Glu101Lys Pathogenic ★★★ same condition
ACTC1 p.Val56Ile Uncertain significance ★★★ ⚠ same condition
ACTC1 p.Ala297Ser Pathogenic ★★ ⚠ same condition
ACTC1 p.Gly247Asp Pathogenic/Likely pathogenic ★★ same condition
ACTC1 p.Thr128Ile Likely pathogenic ★★ same condition
ACTC1 c.455-6G>A Uncertain significance ★★ same condition
ACTC1 c.808+1G>C Uncertain significance ★★ same condition
ACTC1 c.808+3G>A 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-lys330 (accessed [today's date]).

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