Is ACTG2 p.Ala205Asp (c.614C>A) pathogenic?

ACTG2 p.Ala205Asp (c.614C>A) is classified Uncertain significance in ACTG2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2020-12-17). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1; Associated with visceral myopathy 1.

What condition is associated with ACTG2 p.Ala205Asp (c.614C>A)?

ACTG2 p.Ala205Asp (c.614C>A) is associated with visceral myopathy 1 (ClinVar).

How common is ACTG2 p.Ala205Asp (c.614C>A) in the general population?

ACTG2 p.Ala205Asp (c.614C>A) is absent from gnomAD v4.1 (gnomAD).

How is Familial visceral myopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ACTG2 p.Ala205Asp (c.614C>A)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

ACTG2 p.Ala205Asp

c.614C>A · rs1680222160 · VCV992909

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,574,386)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

visceral myopathy 1

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 5% in ACTG2
REVEL	0.945	strongly pathogenic-leaning
SaProt	LLR -11.72	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 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 18 kb · p 3.5e-30 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,574,386). 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: ACTG2
Protein: p.Ala205Asp
Coding: c.614C>A
MANE Select: NM_001615
dbSNP: rs1680222160
Type: single nucleotide variant
Location: chr2:73914680 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 95.46 · 4 PDB
Residue 205: an α-helix

Full ACTG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

visceral myopathy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial visceral myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

ACTG2 p.Ala205Thr Pathogenic ★★ same residue
ACTG2 p.Ala205Val Uncertain significance ★ ⚠ same residue
ACTG2 p.Ala205= Likely benign ★ same residue
ACTG2 p.Arg148Cys Likely pathogenic ★★ same condition
ACTG2 p.Arg178Cys Pathogenic ★★ same condition
ACTG2 p.Arg178His Pathogenic ★★ same condition
ACTG2 p.Arg178Leu Pathogenic ★★ same condition
ACTG2 p.Arg211Gln Pathogenic/Likely 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/actg2-p-ala205asp (accessed [today's date]).

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