Is ACTL10 p.His28= (c.84C>T) pathogenic?

ACTL10 p.His28= (c.84C>T) is classified Likely benign in ACTL10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). Ultra-rare (popmax 0.0169%, mid).

How common is ACTL10 p.His28= (c.84C>T) in the general population?

ACTL10 p.His28= (c.84C>T) is ultra-rare (popmax 0.0169%, mid) (gnomAD).

ACTL10 p.His28=

c.84C>T · VCV4637102

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

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 -5.8	GERP -2
Overall
CADD	11.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% Middle Eastern · 1/5,928 alleles

Filtering AF 0.00062% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000232%

Overall 0.000511% 8/1,566,764 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,928
Admixed American	0.00374%	26,740
African / African-American	0.00271%	36,849
East Asian	0.0024%	41,724
South Asian	0.00115%	86,844
European (non-Finnish)	8.62e-05%	1,159,518

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: ACTL10
Protein: p.His28=
Coding: c.84C>T
MANE Select: NM_001024675
Type: single nucleotide variant
Location: chr20:33667581 (GRCh38)
Gene constraint: LOEUF 1.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.57

Full ACTL10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTL10 p.Ala136Val Uncertain significance ★ ⚠ same type
ACTL10 p.Ala176Pro Uncertain significance ★ ⚠ same type
ACTL10 p.Ala193Glu Uncertain significance ★ ⚠ same type
ACTL10 p.Ala193Pro Uncertain significance ★ ⚠ same type
ACTL10 p.Ala22Ser Uncertain significance ★ ⚠ same type
ACTL10 p.Ala24Val Uncertain significance ★ ⚠ same type
ACTL10 p.Ala2Gly Uncertain significance ★ ⚠ same type
ACTL10 p.Ala34Glu Uncertain significance ★ ⚠ same type

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/actl10-p-his28 (accessed [today's date]).

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