Is ACTB p.Asn12Ser (c.35A>G) pathogenic?

ACTB p.Asn12Ser (c.35A>G) is classified Conflicting classifications of pathogenicity in ACTB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-06-24). AlphaMissense: ambiguous (0.4496); Absent from gnomAD v4.1; Associated with Baraitser-Winter syndrome 1.

What condition is associated with ACTB p.Asn12Ser (c.35A>G)?

ACTB p.Asn12Ser (c.35A>G) is associated with Baraitser-Winter syndrome 1 (ClinVar).

How common is ACTB p.Asn12Ser (c.35A>G) in the general population?

ACTB p.Asn12Ser (c.35A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTB p.Asn12Ser (c.35A>G)?

AlphaMissense predicts ambiguous (score 0.4496) — an in-silico prediction, not a clinical call.

ACTB p.Asn12Ser

c.35A>G · VCV3632540

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4496 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,436)

Conditions

Baraitser-Winter syndrome 1

Computational evidence

Protein change
AlphaMissense	0.4496	ambiguous
REVEL	0.643	indeterminate
SaProt	LLR -11.86	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 289 bp · p 4.5e-15 · regional, not allelic
Overall
CADD	24.9	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

No allele count reported in gnomAD v4.1 (AN 1,611,436). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACTB
Protein: p.Asn12Ser
Coding: c.35A>G
MANE Select: NM_001101
Type: single nucleotide variant
Location: chr7:5529623 (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

Similar variants

ACTB p.Asn12= Likely benign ★★ 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-asn12ser (accessed [today's date]).

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