Is ACTB p.Asn12= (c.36C>T) pathogenic?

ACTB p.Asn12= (c.36C>T) is classified Likely benign in ACTB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-20). Very rare (popmax 0.00668%, afr); Associated with Baraitser-Winter syndrome 1.

What condition is associated with ACTB p.Asn12= (c.36C>T)?

ACTB p.Asn12= (c.36C>T) is associated with Baraitser-Winter syndrome 1, developmental malformations-deafness-dystonia syndrome (ClinVar).

How common is ACTB p.Asn12= (c.36C>T) in the general population?

ACTB p.Asn12= (c.36C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

ACTB p.Asn12=

c.36C>T · rs764325153 · VCV390737

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Conditions

Baraitser-Winter syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -4.2
Overall
CADD	9.794	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,880 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.0023% 37/1,611,334 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,976
European (non-Finnish)	0.00254%	39,325
East Asian	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,334

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.Asn12=
Coding: c.36C>T
MANE Select: NM_001101
dbSNP: rs764325153
Type: single nucleotide variant
Location: chr7:5529622 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 12: a UniProt-annotated variant site (in brws1); a β-strand

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

Disease context

Baraitser-Winter syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental malformations-deafness-dystonia syndrome

Similar variants

ACTB p.Asn12Ser Conflicting classifications of pathogenicity ★ same residue
ACTB p.Asn12Asp Pathogenic same residue
ACTB p.Asn12His Pathogenic same residue
ACTB p.Ala22Thr Likely pathogenic ★★ same condition
ACTB p.Ala7Thr Likely pathogenic ★★ same condition
ACTB p.Arg147Cys Pathogenic ★★ same condition
ACTB p.Arg183Trp Pathogenic ★★ same condition
ACTB p.Arg196Cys 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-asn12 (accessed [today's date]).

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