Is CHST6 p.Ser167Phe (c.500C>T) pathogenic?

CHST6 p.Ser167Phe (c.500C>T) is classified Uncertain significance in CHST6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-22). AlphaMissense: likely benign (0.2466); Ultra-rare (popmax 0.0274%, sas); Associated with macular corneal dystrophy.

What condition is associated with CHST6 p.Ser167Phe (c.500C>T)?

CHST6 p.Ser167Phe (c.500C>T) is associated with macular corneal dystrophy (ClinVar).

How common is CHST6 p.Ser167Phe (c.500C>T) in the general population?

CHST6 p.Ser167Phe (c.500C>T) is ultra-rare (popmax 0.0274%, sas) (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.Ser167Phe (c.500C>T)?

AlphaMissense predicts likely benign (score 0.2466) — an in-silico prediction, not a clinical call.

CHST6 p.Ser167Phe

c.500C>T · rs756399261 · VCV1002002

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2466 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

macular corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.2466	likely benign
REVEL	0.631	indeterminate
SaProt	LLR -7.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP -0.2, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 1,184 bp · p 3.9e-06 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0274% South Asian · 25/91,084 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00446% 72/1,612,778 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0274%	3,643
Middle Eastern	0.0164%	6,084
European (non-Finnish)	0.00364%	27,436
Remaining individualsnot grpmax-eligible	0.0032%	31,229
East Asian	0.00223%	44,866

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.Ser167Phe
Coding: c.500C>T
MANE Select: NM_021615
dbSNP: rs756399261
Type: single nucleotide variant
Location: chr16:75479329 (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-ser167phe (accessed [today's date]).

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