Is VMA21 p.Arg3= (c.9C>T) pathogenic?

VMA21 p.Arg3= (c.9C>T) is classified Likely benign in VMA21 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-01). Very rare (popmax 0.00258%, amr); Associated with X-linked myopathy with excessive autophagy.

What condition is associated with VMA21 p.Arg3= (c.9C>T)?

VMA21 p.Arg3= (c.9C>T) is associated with X-linked myopathy with excessive autophagy (ClinVar).

How common is VMA21 p.Arg3= (c.9C>T) in the general population?

VMA21 p.Arg3= (c.9C>T) is very rare (popmax 0.00258%, amr) (gnomAD).

How is X-linked myopathy with excessive autophagy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

VMA21 p.Arg3=

c.9C>T · rs1268375952 · VCV2729321

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00258%, amr)

Conditions

X-linked myopathy with excessive autophagy

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 -0.33	GERP -1.5
Overall
CADD	9.356	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00258% Admixed American · 1/38,818 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000163%

Overall 0.000603% 7/1,160,992 alleles · very rare exomes 4/1,047,745 · genomes 3/113,247 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00258%	38,818
European (non-Finnish)	0.000688%	145,415

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: VMA21
Protein: p.Arg3=
Coding: c.9C>T
MANE Select: NM_001017980
dbSNP: rs1268375952
Type: single nucleotide variant
Location: chrX:151397317 (GRCh38)
Structure: AlphaFold pLDDT 70.41

Full VMA21 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked myopathy with excessive autophagy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked myopathy with excessive autophagy (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal

Similar variants

VMA21 p.Arg3Leu Uncertain significance ★ ⚠ same residue
VMA21 c.163+4A>G Pathogenic ★★ same condition
VMA21 c.53+5C>T Uncertain significance ★★ same condition
VMA21 p.Ala56Thr Uncertain significance ★★ ⚠ same condition
VMA21 p.Ala68Ser Uncertain significance ★★ ⚠ same condition
VMA21 p.Ala75Thr Uncertain significance ★★ ⚠ same condition
VMA21 p.Ala8Thr Uncertain significance ★★ ⚠ same condition
VMA21 p.Ile42Val 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/vma21-p-arg3 (accessed [today's date]).

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