Is ACTB p.Pro70= (c.210C>T) pathogenic?

ACTB p.Pro70= (c.210C>T) is classified Likely benign in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-11). Very rare (popmax 0.0011%, sas); Associated with Baraitser-Winter syndrome 1.

What condition is associated with ACTB p.Pro70= (c.210C>T)?

ACTB p.Pro70= (c.210C>T) is associated with Baraitser-Winter syndrome 1 (ClinVar).

How common is ACTB p.Pro70= (c.210C>T) in the general population?

ACTB p.Pro70= (c.210C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

ACTB p.Pro70=

c.210C>T · rs758427319 · VCV697053

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 0.025	GERP -4, phastCons 0.41
Overall
CADD	10.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,096 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000682% 11/1,613,940 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,096
European (non-Finnish)	0.000847%	118,004

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.Pro70=
Coding: c.210C>T
MANE Select: NM_001101
dbSNP: rs758427319
Type: single nucleotide variant
Location: chr7:5529314 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 70: a UniProt-annotated variant site (in brws1; likely pathogenic); 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.Pro70Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ACTB p.Pro70His Uncertain significance ⚠ same residue
ACTB p.Pro70Thr 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-pro70 (accessed [today's date]).

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