Is CHST6 p.Arg240Ser (c.718C>A) pathogenic?

CHST6 p.Arg240Ser (c.718C>A) is classified Uncertain significance in CHST6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-14). AlphaMissense: likely benign (0.1269); Ultra-rare (popmax 0.033%, sas); Associated with Inborn genetic diseases.

What condition is associated with CHST6 p.Arg240Ser (c.718C>A)?

CHST6 p.Arg240Ser (c.718C>A) is associated with Inborn genetic diseases, macular corneal dystrophy (ClinVar).

How common is CHST6 p.Arg240Ser (c.718C>A) in the general population?

CHST6 p.Arg240Ser (c.718C>A) is ultra-rare (popmax 0.033%, sas) (gnomAD).

What do computational predictors say about CHST6 p.Arg240Ser (c.718C>A)?

AlphaMissense predicts likely benign (score 0.1269) — an in-silico prediction, not a clinical call.

CHST6 p.Arg240Ser

c.718C>A · rs547928453 · VCV320608

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1269 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1269	likely benign
REVEL	0.496	indeterminate
SaProt	LLR -6.02	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 7.4	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	19.56	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 0.033% South Asian · 30/90,954 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00206% 33/1,605,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.033%	3,032
Middle Eastern	0.0165%	6,056
Remaining individualsnot grpmax-eligible	0.00321%	31,161

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.Arg240Ser
Coding: c.718C>A
MANE Select: NM_021615
dbSNP: rs547928453
Type: single nucleotide variant
Location: chr16:75479111 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: macular corneal dystrophy

Similar variants

CHST6 p.Arg240His Uncertain significance ★ ⚠ same residue
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

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-arg240ser (accessed [today's date]).

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