Is ACTG1 p.Cys285Tyr (c.854G>A) pathogenic?

ACTG1 p.Cys285Tyr (c.854G>A) is classified Uncertain significance in ACTG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-06-27). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACTG1 p.Cys285Tyr (c.854G>A)?

ACTG1 p.Cys285Tyr (c.854G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACTG1 p.Cys285Tyr (c.854G>A) in the general population?

ACTG1 p.Cys285Tyr (c.854G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTG1 p.Cys285Tyr (c.854G>A)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

ACTG1 p.Cys285Tyr

c.854G>A · rs2031734005 · VCV986274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic · top 4% in ACTG1
REVEL	0.918	moderately pathogenic-leaning
SaProt	LLR -12.22	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 3.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 397 bp · p 8e-16 · regional, not allelic
Overall
CADD	25.8	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

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: ACTG1
Protein: p.Cys285Tyr
Coding: c.854G>A
MANE Select: NM_001614
dbSNP: rs2031734005
Type: single nucleotide variant
Location: chr17:81511057 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACTG1 p.Cys285Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
ACTG1 p.Cys285= Likely benign ★ same residue
ACTG1 p.Arg335His Pathogenic/Likely pathogenic ★★ same condition
ACTG1 p.Ala174Ser Uncertain significance ★★ ⚠ same condition
ACTG1 p.His87Tyr Uncertain significance ★★ ⚠ same condition
ACTG1 p.Ile192Val Uncertain significance ★★ ⚠ same condition
ACTG1 p.Ser232Phe Uncertain significance ★★ ⚠ same condition
ACTG1 p.Thr126Ile 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/actg1-p-cys285tyr (accessed [today's date]).

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