Is ACTB p.Asn111Asp (c.331A>G) pathogenic?

ACTB p.Asn111Asp (c.331A>G) is classified Likely pathogenic in ACTB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-03-14). AlphaMissense: likely pathogenic (0.9984); Absent from gnomAD v4.1; Associated with congenital smooth muscle hamartoma.

What condition is associated with ACTB p.Asn111Asp (c.331A>G)?

ACTB p.Asn111Asp (c.331A>G) is associated with congenital smooth muscle hamartoma (ClinVar).

How common is ACTB p.Asn111Asp (c.331A>G) in the general population?

ACTB p.Asn111Asp (c.331A>G) is absent from gnomAD v4.1 (gnomAD).

How is Congenital smooth muscle hamartoma inherited?

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

What do computational predictors say about ACTB p.Asn111Asp (c.331A>G)?

AlphaMissense predicts likely pathogenic (score 0.9984) — an in-silico prediction, not a clinical call.

ACTB p.Asn111Asp

c.331A>G · rs2128241389 · VCV1344714

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9984 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital smooth muscle hamartoma

Computational evidence

Protein change
AlphaMissense	0.9984	likely pathogenic ✓ concordant with ClinVar
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -11.83	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 2.1, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 180 bp · p 1.4e-19 · 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.Asn111Asp
Coding: c.331A>G
MANE Select: NM_001101
dbSNP: rs2128241389
Type: single nucleotide variant
Location: chr7:5529193 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 111: a UniProt-annotated variant site (in csmh; uncertain significance; somatic variant)

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

Disease context

congenital smooth muscle hamartoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital smooth muscle hamartoma (Orphanet):

Inheritance: Not applicable
Onset: Infancy, Neonatal
Prevalence: 1-5 / 10 000 (Israel)

Similar variants

ACTB p.Asn111Ser Likely pathogenic same residue
ACTB p.Arg147Ser 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.Ala22Thr Likely pathogenic ★★ same type
ACTB p.Ala7Thr Likely pathogenic ★★ same type
ACTB p.Arg147Cys 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-asn111asp (accessed [today's date]).

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