Is CHST6 p.Leu15Phe (c.43C>T) pathogenic?

CHST6 p.Leu15Phe (c.43C>T) is classified Uncertain significance in CHST6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: likely benign (0.088); Very rare (popmax 0.00536%, afr); Associated with Inborn genetic diseases.

What condition is associated with CHST6 p.Leu15Phe (c.43C>T)?

CHST6 p.Leu15Phe (c.43C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHST6 p.Leu15Phe (c.43C>T) in the general population?

CHST6 p.Leu15Phe (c.43C>T) is very rare (popmax 0.00536%, afr) (gnomAD).

What do computational predictors say about CHST6 p.Leu15Phe (c.43C>T)?

AlphaMissense predicts likely benign (score 0.088) — an in-silico prediction, not a clinical call.

CHST6 p.Leu15Phe

c.43C>T · VCV4002786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.088 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00536%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.088	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP -0.34, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 1,184 bp · p 3.9e-06 · regional, not allelic
Overall
CADD	18.77	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 0.00536% African / African-American · 4/74,680 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000315% 5/1,586,112 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00536%	18,670
Remaining individualsnot grpmax-eligible	0.00163%	61,532

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.Leu15Phe
Coding: c.43C>T
MANE Select: NM_021615
Type: single nucleotide variant
Location: chr16:75479786 (GRCh38)
Gene constraint: LOEUF 1.71 · pLI 0.26 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.66
Residue 15: a UniProt-annotated variant site (in mcd)

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

Similar variants

CHST6 p.Leu15Ile Uncertain significance ★ ⚠ same residue
CHST6 p.Leu15= Likely benign ★ same residue
CHST6 p.Ala286Val Uncertain significance ★★ ⚠ same condition
CHST6 p.Ala352Val Uncertain significance ★★ ⚠ same condition
CHST6 p.Arg240Ser Uncertain significance ★★ ⚠ same condition
CHST6 p.Arg267Cys Uncertain significance ★★ ⚠ same condition
CHST6 p.Arg344Cys Uncertain significance ★★ ⚠ same condition
CHST6 p.Gln82Pro Uncertain significance ★★ ⚠ 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-leu15phe (accessed [today's date]).

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