Is ACTL10 p.Cys27Arg (c.79T>C) pathogenic?

ACTL10 p.Cys27Arg (c.79T>C) is classified Uncertain significance in ACTL10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: likely pathogenic (0.9544); Absent from gnomAD v4.1.

How common is ACTL10 p.Cys27Arg (c.79T>C) in the general population?

ACTL10 p.Cys27Arg (c.79T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTL10 p.Cys27Arg (c.79T>C)?

AlphaMissense predicts likely pathogenic (score 0.9544) — an in-silico prediction, not a clinical call.

ACTL10 p.Cys27Arg

c.79T>C · VCV4001744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9544 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9544	likely pathogenic · top 1% in ACTL10
REVEL	0.233	benign-leaning
SaProt	LLR -14.34	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 4.6, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 734 bp · p 0.0047 · regional, not allelic
Overall
CADD	27.9	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: ACTL10
Protein: p.Cys27Arg
Coding: c.79T>C
MANE Select: NM_001024675
Type: single nucleotide variant
Location: chr20:33667576 (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-cys27arg (accessed [today's date]).

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