Is ACTA1 p.Asp290Asn (c.868G>A) pathogenic?

ACTA1 p.Asp290Asn (c.868G>A) is classified Pathogenic in ACTA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2009-06-09). AlphaMissense: likely pathogenic (0.9978); Absent from gnomAD v4.1; Associated with nemaline myopathy.

What condition is associated with ACTA1 p.Asp290Asn (c.868G>A)?

ACTA1 p.Asp290Asn (c.868G>A) is associated with nemaline myopathy (ClinVar).

How common is ACTA1 p.Asp290Asn (c.868G>A) in the general population?

ACTA1 p.Asp290Asn (c.868G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTA1 p.Asp290Asn (c.868G>A)?

AlphaMissense predicts likely pathogenic (score 0.9978) — an in-silico prediction, not a clinical call.

ACTA1 p.Asp290Asn

c.868G>A · rs1553255354 · VCV2582806

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nemaline myopathy

Computational evidence

Protein change
AlphaMissense	0.9978	likely pathogenic ✓ concordant with ClinVar
REVEL	0.879	moderately pathogenic-leaning
SaProt	LLR -13.46	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 1,613 bp · p 1.6e-54 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: ACTA1
Protein: p.Asp290Asn
Coding: c.868G>A
MANE Select: NM_001100
dbSNP: rs1553255354
Type: single nucleotide variant
Location: chr1:229431843 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.21 · 5 PDB
Residue 290: a turn

Full ACTA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nemaline myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACTA1 p.Asp290His Pathogenic ★★★ same residue
ACTA1 p.Glu59Lys Likely pathogenic ★★★ same condition
ACTA1 p.Gly148Val Likely pathogenic ★★★ same condition
ACTA1 p.Met229Thr Pathogenic ★★★ same condition
ACTA1 p.Glu255Gln Likely pathogenic ★★ same condition
ACTA1 p.Ala116Pro Likely pathogenic ★ same condition
ACTA1 p.Arg258Gly Likely pathogenic ★ same condition
ACTA1 p.Asp156His Pathogenic ★ 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/acta1-p-asp290asn (accessed [today's date]).

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