Is CHST1 p.Val210Met (c.628G>A) pathogenic?

CHST1 p.Val210Met (c.628G>A) is classified Uncertain significance in CHST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: ambiguous (0.3939); Ultra-rare (popmax 0.0133%, amr).

How common is CHST1 p.Val210Met (c.628G>A) in the general population?

CHST1 p.Val210Met (c.628G>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about CHST1 p.Val210Met (c.628G>A)?

AlphaMissense predicts ambiguous (score 0.3939) — an in-silico prediction, not a clinical call.

CHST1 p.Val210Met

c.628G>A · rs746564532 · VCV2216676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3939 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Computational evidence

Protein change
AlphaMissense	0.3939	ambiguous
REVEL	0.565	indeterminate
SaProt	LLR -4.91	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP -3, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 1,232 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	24.6	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 0.0133% Admixed American · 8/59,958 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000561% 9/1,605,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,495
East Asian	0.00223%	44,762

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: CHST1
Protein: p.Val210Met
Coding: c.628G>A
MANE Select: NM_003654
dbSNP: rs746564532
Type: single nucleotide variant
Location: chr11:45650296 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 87.90

Full CHST1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST1 p.Arg59His Uncertain significance ★★ ⚠ same type
CHST1 p.Ala12Thr Uncertain significance ★ ⚠ same type
CHST1 p.Ala388Thr Uncertain significance ★ ⚠ same type
CHST1 p.Ala43Val Uncertain significance ★ ⚠ same type
CHST1 p.Ala54Thr Uncertain significance ★ ⚠ same type
CHST1 p.Arg114Gln Uncertain significance ★ ⚠ same type
CHST1 p.Arg198Ser Uncertain significance ★ ⚠ same type
CHST1 p.Arg217His Uncertain significance ★ ⚠ 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/chst1-p-val210met (accessed [today's date]).

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