Is ACTB p.Phe90del (c.269_271del) pathogenic?

ACTB p.Phe90del (c.269271del) is classified Conflicting classifications of pathogenicity in ACTB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-20). Absent from gnomAD; Associated with Baraitser-Winter syndrome 1.

What condition is associated with ACTB p.Phe90del (c.269_271del)?

ACTB p.Phe90del (c.269_271del) is associated with Baraitser-Winter syndrome 1 (ClinVar).

How common is ACTB p.Phe90del (c.269_271del) in the general population?

ACTB p.Phe90del (c.269_271del) is absent from gnomAD (gnomAD).

ACTB p.Phe90del

c.269_271del · rs1554329546 · VCV488462

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Phe90del
Coding: c.269_271del
MANE Select: NM_001101
dbSNP: rs1554329546
Type: Deletion
Location: chr7:5529253 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 90: an α-helix

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.Phe90= Likely benign ★★ same residue
ACTB p.Leu110fs Pathogenic ★ same condition
ACTB p.Ala181_Leu185del Uncertain significance ★ same condition
ACTB p.Asp222_Phe223del Uncertain significance ★ same condition
ACTB p.Gln225fs Uncertain significance ★ same condition
ACTB p.Gln263fs Uncertain significance ★ same condition
ACTB p.Leu171_Ala174del Uncertain significance ★ same condition
ACTB p.Lys315del 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-phe90del (accessed [today's date]).

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