Is CHST6 p.Pro72Ser (c.214C>T) pathogenic?

CHST6 p.Pro72Ser (c.214C>T) is classified Uncertain significance in CHST6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-03). AlphaMissense: likely pathogenic (0.9413); Very rare (popmax 0.004%, afr).

How common is CHST6 p.Pro72Ser (c.214C>T) in the general population?

CHST6 p.Pro72Ser (c.214C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CHST6 p.Pro72Ser (c.214C>T)?

AlphaMissense predicts likely pathogenic (score 0.9413) — an in-silico prediction, not a clinical call.

CHST6 p.Pro72Ser

c.214C>T · VCV3336188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9413 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9413	likely pathogenic · top 8% in CHST6
REVEL	0.972	strongly pathogenic-leaning
SaProt	LLR -14.05	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 12	GERP 2, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 1,184 bp · p 3.9e-06 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.004% African / African-American · 3/74,942 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,612,776 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,981
European (non-Finnish)	8.48e-05%	1,179,866

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.Pro72Ser
Coding: c.214C>T
MANE Select: NM_021615
Type: single nucleotide variant
Location: chr16:75479615 (GRCh38)
Gene constraint: LOEUF 1.71 · pLI 0.26 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.66
Residue 72: a UniProt-annotated variant site (in mcd)

Full CHST6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST6 p.Ala128Thr Likely pathogenic ★★ ⚠ same type
CHST6 p.Arg127Cys Pathogenic ★★ same type
CHST6 p.Arg140Ter Pathogenic ★★ same type
CHST6 p.Arg211Gln Pathogenic ★★ ⚠ same type
CHST6 p.Cys102Gly Pathogenic ★★ same type
CHST6 p.Gln58Ter Pathogenic/Likely pathogenic ★★ same type
CHST6 p.Glu274Lys Pathogenic ★★ same type
CHST6 p.Leu200Arg Pathogenic ★★ same type

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-pro72ser (accessed [today's date]).

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