Is CHST6 p.Arg40= (c.120C>T) pathogenic?

CHST6 p.Arg40= (c.120C>T) is classified Benign in CHST6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-31). Low-frequency (popmax 3.26%, afr); Associated with macular corneal dystrophy.

What condition is associated with CHST6 p.Arg40= (c.120C>T)?

CHST6 p.Arg40= (c.120C>T) is associated with macular corneal dystrophy (ClinVar).

How common is CHST6 p.Arg40= (c.120C>T) in the general population?

CHST6 p.Arg40= (c.120C>T) is low-frequency (popmax 3.26%, afr) (gnomAD).

How is Macular corneal dystrophy inherited?

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

CHST6 p.Arg40=

c.120C>T · rs61740904 · VCV320615

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.26%, afr)

Conditions

macular corneal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.2	GERP -3.8
Overall
CADD	0.199	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.26% African / African-American · 2,446/74,984 alleles

Filtering AF 3.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.11%

Overall 0.172% 2,763/1,609,842 alleles · low-frequency exomes 1,329/1,457,534 · genomes 1,434/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.26%	31
Remaining individualsnot grpmax-eligible	0.257%	390
Admixed American	0.191%	523
Middle Eastern	0.149%	673
South Asian	0.0143%	6,984
European (non-Finnish)	0.00178%	56,106

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.Arg40=
Coding: c.120C>T
MANE Select: NM_021615
dbSNP: rs61740904
Type: single nucleotide variant
Location: chr16:75479709 (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-arg40 (accessed [today's date]).

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