Is ACTB p.Arg147Ser (c.439C>A) pathogenic?

ACTB p.Arg147Ser (c.439C>A) is classified Pathogenic in ACTB (ClinVar, Single submitter, 3 submitters; last evaluated 2024-08-19). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with Becker nevus syndrome.

What condition is associated with ACTB p.Arg147Ser (c.439C>A)?

ACTB p.Arg147Ser (c.439C>A) is associated with Becker nevus syndrome, congenital smooth muscle hamartoma (ClinVar).

How common is ACTB p.Arg147Ser (c.439C>A) in the general population?

ACTB p.Arg147Ser (c.439C>A) is absent from gnomAD v4.1 (gnomAD).

How is Becker nevus syndrome inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ACTB p.Arg147Ser (c.439C>A)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

ACTB p.Arg147Ser

c.439C>A · rs2128241302 · VCV1344710

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Becker nevus syndrome

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 7% in ACTB
REVEL	0.86	moderately pathogenic-leaning
SaProt	LLR -13.60	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 4.6	GERP 0.78, phastCons 1
Regional constraint	o/e 0.11	constrained · MANE · 1,149 bp · p 1.6e-51 · regional, not allelic
Overall
CADD	33.0	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

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.Arg147Ser
Coding: c.439C>A
MANE Select: NM_001101
dbSNP: rs2128241302
Type: single nucleotide variant
Location: chr7:5528644 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 147: a UniProt-annotated variant site (in bns and csmh; also found in isolated non-syndromic becker nevi; somatic variant); a UniProt-annotated variant site (in csmh; also found in isolated non-syndromic becker nevi; somatic variant)

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

Disease context

Becker nevus syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital smooth muscle hamartoma

For Becker nevus syndrome (Orphanet):

Inheritance: Not applicable
Onset: All ages

Similar variants

ACTB p.Arg147Cys Pathogenic ★★ same residue
ACTB p.Arg147His Uncertain significance ★ ⚠ same residue
ACTB p.Met283Thr Uncertain significance ★ ⚠ same condition
ACTB p.Asn111Asp Likely pathogenic same condition
ACTB p.Gln137His Likely pathogenic same condition
ACTB p.Gly146Ala Pathogenic/Likely pathogenic same condition
ACTB p.Gly146Ser Pathogenic/Likely pathogenic same condition
ACTB p.Thr148_Thr149insLeuTyrAlaSerGlyArgThr 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/actb-p-arg147ser (accessed [today's date]).

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