Is ACTB p.Asp187fs (c.559_562del) pathogenic?

ACTB p.Asp187fs (c.559562del) is classified Conflicting classifications of pathogenicity in ACTB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-06). Absent from gnomAD; Associated with Baraitser-Winter syndrome 1.

What condition is associated with ACTB p.Asp187fs (c.559_562del)?

ACTB p.Asp187fs (c.559_562del) is associated with Baraitser-Winter syndrome 1 (ClinVar).

How common is ACTB p.Asp187fs (c.559_562del) in the general population?

ACTB p.Asp187fs (c.559_562del) is absent from gnomAD (gnomAD).

ACTB p.Asp187fs

c.559_562del · rs886041265 · VCV279937

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 0.87, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Asp187fs
Coding: c.559_562del
MANE Select: NM_001101
dbSNP: rs886041265
Type: Microsatellite
Location: chr7:5528521 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 187: 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.Asp187= Likely benign ★ same residue
ACTB p.Asp4del Uncertain significance ★★ same condition
ACTB p.Asp187Glu Uncertain significance ★ ⚠ same residue
ACTB c.124-11TTCC[3] Likely benign ★ same condition
ACTB c.124-19_124-17del Likely benign ★ same condition
ACTB c.985-5_985-3del Likely benign ★ same condition
ACTB p.Ala22Thr Likely pathogenic ★★ same condition
ACTB p.Ala7Thr 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-asp187fs (accessed [today's date]).

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