Is CHST6 p.Val43= (c.129G>A) pathogenic?

CHST6 p.Val43= (c.129G>A) is classified Benign/Likely benign in CHST6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-18). Low-frequency (popmax 1.15%, afr); Associated with macular corneal dystrophy.

What condition is associated with CHST6 p.Val43= (c.129G>A)?

CHST6 p.Val43= (c.129G>A) is associated with macular corneal dystrophy (ClinVar).

How common is CHST6 p.Val43= (c.129G>A) in the general population?

CHST6 p.Val43= (c.129G>A) is low-frequency (popmax 1.15%, afr) (gnomAD).

How is Macular corneal dystrophy inherited?

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

CHST6 p.Val43=

c.129G>A · rs112939575 · VCV320614

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, afr)

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 1.4	GERP 1, phastCons 1
Overall
CADD	7.899	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.15% African / African-American · 862/75,024 alleles

Filtering AF 1.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.06%

Overall 0.0634% 1,022/1,611,396 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.15%	87
Admixed American	0.124%	809
Remaining individualsnot grpmax-eligible	0.0705%	1,418
Middle Eastern	0.033%	3,028
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,900
European (non-Finnish)	0.00297%	33,688

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.Val43=
Coding: c.129G>A
MANE Select: NM_021615
dbSNP: rs112939575
Type: single nucleotide variant
Location: chr16:75479700 (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-val43 (accessed [today's date]).

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