Is ACTB p.Ser60= (c.180C>T) pathogenic?

ACTB p.Ser60= (c.180C>T) is classified Conflicting classifications of pathogenicity in ACTB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0251%, nfe); Associated with developmental malformations-deafness-dystonia syndrome.

How common is ACTB p.Ser60= (c.180C>T) in the general population?

ACTB p.Ser60= (c.180C>T) is ultra-rare (popmax 0.0251%, nfe) (gnomAD).

ACTB p.Ser60=

Q: What condition is associated with ACTB p.Ser60= (c.180C>T)?

ACTB p.Ser60= (c.180C>T) is associated with developmental malformations-deafness-dystonia syndrome, Baraitser-Winter syndrome 1 (ClinVar).

c.180C>T · rs147566416 · VCV645776

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0251%, nfe)

Conditions

developmental malformations-deafness-dystonia syndrome

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 6.5	GERP -0.15, phastCons 1
Overall
CADD	14.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0251% European (non-Finnish) · 296/1,180,044 alleles

Filtering AF 0.0227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0217%

Overall 0.0186% 301/1,613,972 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0251%	3,987
Remaining individualsnot grpmax-eligible	0.008%	12,497

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.Ser60=
Coding: c.180C>T
MANE Select: NM_001101
dbSNP: rs147566416
Type: single nucleotide variant
Location: chr7:5529344 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 60: an α-helix

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

Disease context

developmental malformations-deafness-dystonia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Baraitser-Winter syndrome 1

Similar variants

ACTB p.Ser60Arg Likely pathogenic ★ same residue
ACTB p.Ser60Asn Likely 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
ACTB p.Arg196His 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-ser60 (accessed [today's date]).

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