Is ACTB p.Glu57Ala (c.170A>C) pathogenic?

ACTB p.Glu57Ala (c.170A>C) is classified Uncertain significance in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-26). AlphaMissense: likely pathogenic (0.9896); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACTB p.Glu57Ala (c.170A>C)?

ACTB p.Glu57Ala (c.170A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ACTB p.Glu57Ala (c.170A>C) in the general population?

ACTB p.Glu57Ala (c.170A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTB p.Glu57Ala (c.170A>C)?

AlphaMissense predicts likely pathogenic (score 0.9896) — an in-silico prediction, not a clinical call.

ACTB p.Glu57Ala

c.170A>C · rs1784832645 · VCV985415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9896 · 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	0.9896	likely pathogenic
REVEL	0.823	moderately pathogenic-leaning
SaProt	LLR -14.98	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 7.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 180 bp · p 1.4e-19 · regional, not allelic
Overall
CADD	26.9	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: ACTB
Protein: p.Glu57Ala
Coding: c.170A>C
MANE Select: NM_001101
dbSNP: rs1784832645
Type: single nucleotide variant
Location: chr7:5529354 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 57: an α-helix

Full ACTB 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

ACTB p.Glu57Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
ACTB p.Arg196His Pathogenic ★★ same condition
ACTB p.Arg206Gln Pathogenic/Likely pathogenic ★★ same condition
ACTB p.Asp179Glu Uncertain significance ★★ ⚠ same condition
ACTB p.Thr229Ala Uncertain significance ★★ ⚠ same condition
ACTB p.Ala260Glu Likely pathogenic ★ same condition
ACTB p.His87Asp Pathogenic ★ same condition
ACTB p.Asn296Ser 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/actb-p-glu57ala (accessed [today's date]).

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