Is ACTB p.His87Asp (c.259C>G) pathogenic?

ACTB p.His87Asp (c.259C>G) is classified Pathogenic in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2016-08-30). AlphaMissense: likely pathogenic (0.998); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACTB p.His87Asp (c.259C>G)?

ACTB p.His87Asp (c.259C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ACTB p.His87Asp (c.259C>G) in the general population?

ACTB p.His87Asp (c.259C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTB p.His87Asp (c.259C>G)?

AlphaMissense predicts likely pathogenic (score 0.998) — an in-silico prediction, not a clinical call.

ACTB p.His87Asp

c.259C>G · rs1554329552 · VCV521266

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.998	likely pathogenic ✓ concordant with ClinVar
REVEL	0.926	moderately pathogenic-leaning
SaProt	LLR -13.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 180 bp · p 1.4e-19 · regional, not allelic
Overall
CADD	33.0	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.His87Asp
Coding: c.259C>G
MANE Select: NM_001101
dbSNP: rs1554329552
Type: single nucleotide variant
Location: chr7:5529265 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACTB p.His87Tyr Uncertain significance ★★ ⚠ same residue
ACTB p.Arg196His Pathogenic ★★ same condition
ACTB p.Arg206Gln Pathogenic/Likely pathogenic ★★ same condition
ACTB p.Asp179Glu Uncertain significance ★★ ⚠ same condition
ACTB p.Thr229Ala Uncertain significance ★★ ⚠ same condition
ACTB p.Ala260Glu Likely pathogenic ★ same condition
ACTB p.Asn296Ser Uncertain significance ★ ⚠ same condition
ACTB p.Glu57Ala 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-his87asp (accessed [today's date]).

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