Is ACTB p.Thr194Ala (c.580A>G) pathogenic?

ACTB p.Thr194Ala (c.580A>G) is classified Uncertain significance in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: ambiguous (0.5503); Very rare (popmax 0.00133%, afr).

How common is ACTB p.Thr194Ala (c.580A>G) in the general population?

ACTB p.Thr194Ala (c.580A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ACTB p.Thr194Ala (c.580A>G)?

AlphaMissense predicts ambiguous (score 0.5503) — an in-silico prediction, not a clinical call.

ACTB p.Thr194Ala

c.580A>G · VCV3368521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5503 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
AlphaMissense	0.5503	ambiguous
REVEL	0.485	indeterminate
SaProt	LLR -11.61	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.11	constrained · MANE · 1,149 bp · p 1.6e-51 · regional, not allelic
Overall
CADD	27.6	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

Grpmax group 0.00133% African / African-American · 1/74,908 alleles

Overall 0.000657% 1/152,124 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ACTB
Protein: p.Thr194Ala
Coding: c.580A>G
MANE Select: NM_001101
Type: single nucleotide variant
Location: chr7:5528503 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 194: an α-helix

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

Similar variants

ACTB p.Thr194= Likely benign ★ same residue
ACTB p.Ala22Thr Likely pathogenic ★★ same type
ACTB p.Ala7Thr Likely pathogenic ★★ same type
ACTB p.Arg147Cys Pathogenic ★★ same type
ACTB p.Arg183Trp Pathogenic ★★ same type
ACTB p.Arg196Cys Pathogenic ★★ same type
ACTB p.Arg196His Pathogenic ★★ same type
ACTB p.Arg196Leu 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/actb-p-thr194ala (accessed [today's date]).

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