Is SELENON p.Pro6= (c.18G>A) pathogenic?

SELENON p.Pro6= (c.18G>A) is classified Likely benign in SELENON (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). Ultra-rare (popmax 0.01%, sas); Associated with congenital myopathy 3 with rigid spine.

What condition is associated with SELENON p.Pro6= (c.18G>A)?

SELENON p.Pro6= (c.18G>A) is associated with congenital myopathy 3 with rigid spine (ClinVar).

How common is SELENON p.Pro6= (c.18G>A) in the general population?

SELENON p.Pro6= (c.18G>A) is ultra-rare (popmax 0.01%, sas) (gnomAD).

SELENON p.Pro6=

Q: How is Desmin-related myopathy with Mallory body-like inclusions inherited?

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

c.18G>A · rs1572226803 · VCV1023267

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, sas)

Conditions

congenital myopathy 3 with rigid spine

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 -2.5	GERP -1.1
Overall
CADD	10.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% South Asian · 2/19,950 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000719%

Overall 0.00034% 3/883,426 alleles · ultra-rare exomes 3/738,930 · genomes 0/144,496 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.01%	9,975
Remaining individualsnot grpmax-eligible	0.00383%	26,092

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: SELENON
Protein: p.Pro6=
Coding: c.18G>A
MANE Select: NM_206926
dbSNP: rs1572226803
Type: single nucleotide variant
Location: chr1:25800248 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 (gnomAD)
Residue 6: the 'disordered' region

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

Disease context

congenital myopathy 3 with rigid spine — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Desmin-related myopathy with Mallory body-like inclusions (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SELENON p.Pro6Ser Likely benign ★ same residue
SELENON c.1285+1G>A Pathogenic/Likely pathogenic ★★ same condition
SELENON c.436-1G>A Likely pathogenic ★★ same condition
SELENON c.770+2T>C Pathogenic/Likely pathogenic ★★ same condition
SELENON c.908+1G>A Pathogenic/Likely pathogenic ★★ same condition
SELENON c.909-1G>C Likely pathogenic ★★ same condition
SELENON c.*1107T>C Pathogenic/Likely pathogenic ★★ same condition
SELENON p.Arg127Ter Pathogenic/Likely pathogenic ★★ 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/selenon-p-pro6 (accessed [today's date]).

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