Is ACTC1 p.Thr280= (c.840T>C) pathogenic?

ACTC1 p.Thr280= (c.840T>C) is classified Likely benign in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-04-06). Absent from gnomAD v4.1.

How common is ACTC1 p.Thr280= (c.840T>C) in the general population?

ACTC1 p.Thr280= (c.840T>C) is absent from gnomAD v4.1 (gnomAD).

ACTC1 p.Thr280=

c.840T>C · rs1057522193 · VCV385329

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.1	GERP -1.2, phastCons 1
Overall
CADD	10.13	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.Thr280=
Coding: c.840T>C
MANE Select: NM_005159
dbSNP: rs1057522193
Type: single nucleotide variant
Location: chr15:34791264 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB
Residue 280: an α-helix

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

Similar variants

ACTC1 p.Thr280Ser Uncertain significance ★ ⚠ same residue
ACTC1 p.Glu101Lys Pathogenic ★★★ same type
ACTC1 p.Gly345Val Uncertain significance ★★★ ⚠ same type
ACTC1 p.Pro266Leu Uncertain significance ★★★ ⚠ same type
ACTC1 p.Val56Ile Uncertain significance ★★★ ⚠ same type
ACTC1 p.Ala297Ser Pathogenic ★★ ⚠ same type
ACTC1 p.Gly247Asp Pathogenic/Likely pathogenic ★★ same type
ACTC1 p.Thr128Ile Likely pathogenic ★★ same type

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-thr280 (accessed [today's date]).

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