Is CHST6 p.Val99fs (c.290_293dup) pathogenic?

CHST6 p.Val99fs (c.290293dup) is classified Pathogenic in CHST6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-07). Absent from gnomAD; Associated with macular corneal dystrophy.

What condition is associated with CHST6 p.Val99fs (c.290_293dup)?

CHST6 p.Val99fs (c.290_293dup) is associated with macular corneal dystrophy (ClinVar).

How common is CHST6 p.Val99fs (c.290_293dup) in the general population?

CHST6 p.Val99fs (c.290_293dup) is absent from gnomAD (gnomAD).

How is Macular corneal dystrophy inherited?

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

CHST6 p.Val99fs

c.290_293dup · rs2507252387 · VCV2026508

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 -16	GERP -4.1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHST6
Protein: p.Val99fs
Coding: c.290_293dup
MANE Select: NM_021615
dbSNP: rs2507252387
Type: Duplication
Location: chr16:75479535 (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.Ala192fs Pathogenic ★ same condition
CHST6 p.Glu163fs Likely pathogenic ★ same condition
CHST6 p.Leu299fs Pathogenic ★ same condition
CHST6 p.Ser98fs Likely pathogenic ★ same condition
CHST6 p.Glu364Ter Conflicting classifications of pathogenicity ★ same condition
CHST6 p.Ala128Thr Likely pathogenic ★★ ⚠ same condition
CHST6 p.Arg127Cys Pathogenic ★★ same condition
CHST6 p.Arg140Ter 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/chst6-p-val99fs (accessed [today's date]).

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