Is CHST6 p.Arg269fs (c.805del) pathogenic?

CHST6 p.Arg269fs (c.805del) is classified Conflicting classifications of pathogenicity in CHST6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-19). Very rare (popmax 0.00017%, nfe); Associated with macular corneal dystrophy.

What condition is associated with CHST6 p.Arg269fs (c.805del)?

CHST6 p.Arg269fs (c.805del) is associated with macular corneal dystrophy (ClinVar).

How common is CHST6 p.Arg269fs (c.805del) in the general population?

CHST6 p.Arg269fs (c.805del) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Macular corneal dystrophy inherited?

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

CHST6 p.Arg269fs

c.805del · VCV3581252

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

macular corneal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.025	GERP -4.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,830 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000206% 3/1,457,976 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,474
European (non-Finnish)grpmax	0.00017%	589,915

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CHST6
Protein: p.Arg269fs
Coding: c.805del
MANE Select: NM_021615
Type: Deletion
Location: chr16:75479024 (GRCh38)
Gene constraint: LOEUF 1.71 · pLI 0.26 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.66

Full CHST6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

macular corneal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Macular corneal dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (United States)

Similar variants

CHST6 p.Arg247fs Likely pathogenic ★ same condition
CHST6 p.Gln18fs Pathogenic ★ same condition
CHST6 p.Gly227fs Pathogenic ★ same condition
CHST6 p.Leu276fs Likely pathogenic ★ same condition
CHST6 p.Lys341fs Likely pathogenic ★ same condition
CHST6 p.Val201_Val207del Pathogenic ★ same condition
CHST6 p.Val233fs Likely pathogenic ★ same condition
CHST6 p.Asn328fs 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/chst6-p-arg269fs (accessed [today's date]).

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