Is CHST6 p.Ala256= (c.768C>T) pathogenic?

CHST6 p.Ala256= (c.768C>T) is classified Benign in CHST6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.39%, nfe); Associated with macular corneal dystrophy.

What condition is associated with CHST6 p.Ala256= (c.768C>T)?

CHST6 p.Ala256= (c.768C>T) is associated with macular corneal dystrophy (ClinVar).

How common is CHST6 p.Ala256= (c.768C>T) in the general population?

CHST6 p.Ala256= (c.768C>T) is low-frequency (popmax 1.39%, nfe) (gnomAD).

How is Macular corneal dystrophy inherited?

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

CHST6 p.Ala256=

c.768C>T · rs146465655 · VCV778124

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.39%, nfe)

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 -0.8	GERP -0.81
Overall
CADD	3.369	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.39% European (non-Finnish) · 16,405/1,179,480 alleles

Filtering AF 1.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.37%

Overall 1.2% 19,233/1,606,646 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.39%	72
Ashkenazi Jewishnot grpmax-eligible	1.17%	85
Remaining individualsnot grpmax-eligible	1.1%	91
Finnishnot grpmax-eligible	1.04%	96
South Asian	0.877%	114
Admixed American	0.373%	268
Middle Eastern	0.297%	337
African / African-American	0.207%	484
East Asian	0.00669%	14,953

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.Ala256=
Coding: c.768C>T
MANE Select: NM_021615
dbSNP: rs146465655
Type: single nucleotide variant
Location: chr16:75479061 (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-ala256 (accessed [today's date]).

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