Is CHST6 p.Ser210Phe (c.629C>T) pathogenic?

CHST6 p.Ser210Phe (c.629C>T) is classified Likely pathogenic in CHST6 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-11). AlphaMissense: likely pathogenic (0.9634); Very rare (popmax 0.005%, nfe); Associated with CHST6-related disorder.

What condition is associated with CHST6 p.Ser210Phe (c.629C>T)?

CHST6 p.Ser210Phe (c.629C>T) is associated with CHST6-related disorder (ClinVar).

How common is CHST6 p.Ser210Phe (c.629C>T) in the general population?

CHST6 p.Ser210Phe (c.629C>T) is very rare (popmax 0.005%, nfe) (gnomAD).

What do computational predictors say about CHST6 p.Ser210Phe (c.629C>T)?

AlphaMissense predicts likely pathogenic (score 0.9634) — an in-silico prediction, not a clinical call.

CHST6 p.Ser210Phe

c.629C>T · VCV4931267

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CHST6-related disorder

Computational evidence

Protein change
AlphaMissense	0.9634	likely pathogenic ✓ concordant with ClinVar · top 6% in CHST6
REVEL	0.974	strongly pathogenic-leaning
SaProt	LLR -15.07	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 9.9	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	25.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% European (non-Finnish) · 59/1,179,194 alleles

Filtering AF 0.00394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.00379% 61/1,609,106 alleles · very rare exomes 59/1,456,910 · genomes 2/152,196 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.005%	19,986
Remaining individualsnot grpmax-eligible	0.0016%	62,368
African / African-American	0.00134%	74,898

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.Ser210Phe
Coding: c.629C>T
MANE Select: NM_021615
Type: single nucleotide variant
Location: chr16:75479200 (GRCh38)
Gene constraint: LOEUF 1.71 · pLI 0.26 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.66
Residue 210: a binding site; a UniProt-annotated variant site (in mcd)

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

Disease context

CHST6-related disorder

Similar variants

CHST6 p.Ala128Thr Likely pathogenic ★★ ⚠ same condition
CHST6 p.Arg127Cys Pathogenic ★★ same condition
CHST6 p.Glu274Lys Pathogenic ★★ same condition
CHST6 p.Leu200Arg Pathogenic ★★ same condition
CHST6 p.Ala128Val Pathogenic ★ same condition
CHST6 p.Ser131Leu Pathogenic ★ same condition
CHST6 p.Val329Leu Pathogenic ★ ⚠ same condition
CHST6 p.Ala13= Likely benign 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-ser210phe (accessed [today's date]).

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