Is ACTL10 p.Lys75Arg (c.224A>G) pathogenic?

ACTL10 p.Lys75Arg (c.224A>G) is classified Uncertain significance in ACTL10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). AlphaMissense: likely benign (0.1051); Ultra-rare (popmax 0.0869%, eas).

How common is ACTL10 p.Lys75Arg (c.224A>G) in the general population?

ACTL10 p.Lys75Arg (c.224A>G) is ultra-rare (popmax 0.0869%, eas) (gnomAD).

What do computational predictors say about ACTL10 p.Lys75Arg (c.224A>G)?

AlphaMissense predicts likely benign (score 0.1051) — an in-silico prediction, not a clinical call.

ACTL10 p.Lys75Arg

c.224A>G · VCV3263794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1051 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0869%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1051	likely benign
REVEL	0.386	indeterminate
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 4.6, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 734 bp · p 0.0047 · regional, not allelic
Overall
CADD	19.26	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0869% East Asian · 39/44,880 alleles

Filtering AF 0.0653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00254% 41/1,612,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0869%	1,151
European (non-Finnish)	0.00017%	589,950

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.Lys75Arg
Coding: c.224A>G
MANE Select: NM_001024675
Type: single nucleotide variant
Location: chr20:33667721 (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-lys75arg (accessed [today's date]).

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