Is CHST6 p.Ser157Pro (c.469T>C) pathogenic?

CHST6 p.Ser157Pro (c.469T>C) is classified Likely benign in CHST6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). AlphaMissense: likely benign (0.0471); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHST6 p.Ser157Pro (c.469T>C)?

CHST6 p.Ser157Pro (c.469T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CHST6 p.Ser157Pro (c.469T>C) in the general population?

CHST6 p.Ser157Pro (c.469T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CHST6 p.Ser157Pro (c.469T>C)?

AlphaMissense predicts likely benign (score 0.0471) — an in-silico prediction, not a clinical call.

CHST6 p.Ser157Pro

c.469T>C · VCV4615564

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0471 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0471	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -3.98	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 8.7	GERP -0.18, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 1,184 bp · p 3.9e-06 · regional, not allelic
Overall
CADD	14.12	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 0.00167% Admixed American · 1/59,992 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000558% 9/1,612,576 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,576
Admixed Americangrpmax	0.00167%	59,992
European (non-Finnish)	0.000593%	168,540

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser157Pro
Coding: c.469T>C
MANE Select: NM_021615
Type: single nucleotide variant
Location: chr16:75479360 (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

Similar variants

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
CHST6 p.Glu317Gln Uncertain significance ★★ ⚠ same condition
CHST6 p.Gly238Asp 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-ser157pro (accessed [today's date]).

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