Is CHST6 p.Pro204Gln (c.611C>A) pathogenic?

CHST6 p.Pro204Gln (c.611C>A) is classified Likely pathogenic in CHST6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely pathogenic (0.9602); Very rare (popmax 0.000678%, nfe); Associated with macular corneal dystrophy.

What condition is associated with CHST6 p.Pro204Gln (c.611C>A)?

CHST6 p.Pro204Gln (c.611C>A) is associated with macular corneal dystrophy (ClinVar).

How common is CHST6 p.Pro204Gln (c.611C>A) in the general population?

CHST6 p.Pro204Gln (c.611C>A) is very rare (popmax 0.000678%, nfe) (gnomAD).

How is Macular corneal dystrophy inherited?

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

What do computational predictors say about CHST6 p.Pro204Gln (c.611C>A)?

AlphaMissense predicts likely pathogenic (score 0.9602) — an in-silico prediction, not a clinical call.

CHST6 p.Pro204Gln

c.611C>A · VCV3366790

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9602 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

macular corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9602	likely pathogenic ✓ concordant with ClinVar · top 6% in CHST6
REVEL	0.967	strongly pathogenic-leaning
SaProt	LLR -17.00	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.1, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 1,184 bp · p 3.9e-06 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,468 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000497% 8/1,610,112 alleles · very rare

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.Pro204Gln
Coding: c.611C>A
MANE Select: NM_021615
Type: single nucleotide variant
Location: chr16:75479218 (GRCh38)
Gene constraint: LOEUF 1.71 · pLI 0.26 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.66
Residue 204: a binding site; a UniProt-annotated variant site (in mcd)

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-pro204gln (accessed [today's date]).

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