Is CHST6 p.Leu101= (c.301C>T) pathogenic?

CHST6 p.Leu101= (c.301C>T) is classified Conflicting classifications of pathogenicity in CHST6 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-29). Rare (popmax 0.104%, sas); Associated with macular corneal dystrophy.

What condition is associated with CHST6 p.Leu101= (c.301C>T)?

CHST6 p.Leu101= (c.301C>T) is associated with macular corneal dystrophy (ClinVar).

How common is CHST6 p.Leu101= (c.301C>T) in the general population?

CHST6 p.Leu101= (c.301C>T) is rare (popmax 0.104%, sas) (gnomAD).

How is Macular corneal dystrophy inherited?

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

CHST6 p.Leu101=

c.301C>T · rs373160858 · VCV886988

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.104%, sas)

Conditions

macular corneal dystrophy

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 4.7	GERP -0.37, phastCons 1
Overall
CADD	5.989	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.104% South Asian · 95/91,084 alleles

Filtering AF 0.0873% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.081%

Overall 0.0315% 508/1,612,974 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.104%	959
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.0317%	3,155
Remaining individualsnot grpmax-eligible	0.0288%	3,471
Admixed American	0.0167%	6,001
Finnishnot grpmax-eligible	0.0111%	9,008
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,588
African / African-American	0.00133%	75,052

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.Leu101=
Coding: c.301C>T
MANE Select: NM_021615
dbSNP: rs373160858
Type: single nucleotide variant
Location: chr16:75479528 (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.Ala128Thr Likely pathogenic ★★ ⚠ same condition
CHST6 p.Arg127Cys Pathogenic ★★ same condition
CHST6 p.Arg140Ter Pathogenic ★★ same condition
CHST6 p.Arg211Gln Pathogenic ★★ ⚠ same condition
CHST6 p.Cys102Gly Pathogenic ★★ same condition
CHST6 p.Gln58Ter Pathogenic/Likely pathogenic ★★ same condition
CHST6 p.Glu274Lys Pathogenic ★★ same condition
CHST6 p.Leu200Arg 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-leu101 (accessed [today's date]).

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