Is ACTB p.His73Gln (c.219C>G) pathogenic?

ACTB p.His73Gln (c.219C>G) is classified Likely pathogenic in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2017-02-14). AlphaMissense: likely pathogenic (0.9882); Absent from gnomAD v4.1; Associated with developmental malformations-deafness-dystonia syndrome.

How common is ACTB p.His73Gln (c.219C>G) in the general population?

ACTB p.His73Gln (c.219C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTB p.His73Gln (c.219C>G)?

AlphaMissense predicts likely pathogenic (score 0.9882) — an in-silico prediction, not a clinical call.

ACTB p.His73Gln

Q: What condition is associated with ACTB p.His73Gln (c.219C>G)?

ACTB p.His73Gln (c.219C>G) is associated with developmental malformations-deafness-dystonia syndrome, Baraitser-Winter syndrome 1 (ClinVar).

c.219C>G · rs1166509821 · VCV620046

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9882 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental malformations-deafness-dystonia syndrome

Computational evidence

Protein change
AlphaMissense	0.9882	likely pathogenic ✓ concordant with ClinVar
REVEL	0.71	pathogenic-leaning
SaProt	LLR -12.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -3.9
Regional constraint	o/e 0.00	constrained · MANE · 180 bp · p 1.4e-19 · regional, not allelic
Overall
CADD	24.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACTB
Protein: p.His73Gln
Coding: c.219C>G
MANE Select: NM_001101
dbSNP: rs1166509821
Type: single nucleotide variant
Location: chr7:5529305 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 73: a modified residue (tele-methylhistidine)

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.His73Tyr Pathogenic/Likely pathogenic ★★ same residue
ACTB p.His73= Likely benign ★ same residue
ACTB p.His73Asp 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

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-his73gln (accessed [today's date]).

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