Is CHST4 p.Phe211Cys (c.632T>G) pathogenic?

CHST4 p.Phe211Cys (c.632T>G) is classified Uncertain significance in CHST4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). AlphaMissense: likely pathogenic (0.5846); Absent from gnomAD v4.1.

How common is CHST4 p.Phe211Cys (c.632T>G) in the general population?

CHST4 p.Phe211Cys (c.632T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHST4 p.Phe211Cys (c.632T>G)?

AlphaMissense predicts likely pathogenic (score 0.5846) — an in-silico prediction, not a clinical call.

CHST4 p.Phe211Cys

c.632T>G · VCV3267231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5846 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5846	likely pathogenic
REVEL	0.708	pathogenic-leaning
SaProt	LLR -10.32	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 7.9	GERP 1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,157 bp · p 0.075 · regional, not allelic
Overall
CADD	27.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHST4
Protein: p.Phe211Cys
Coding: c.632T>G
MANE Select: NM_001166395
Type: single nucleotide variant
Location: chr16:71537309 (GRCh38)
Gene constraint: LOEUF 1.836 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 90.66
Residue 211: a binding site

Full CHST4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST4 p.Ala135Val Uncertain significance ★ ⚠ same type
CHST4 p.Ala167Ser Uncertain significance ★ ⚠ same type
CHST4 p.Ala18Ser Uncertain significance ★ ⚠ same type
CHST4 p.Ala18Thr Uncertain significance ★ ⚠ same type
CHST4 p.Ala333Val Uncertain significance ★ ⚠ same type
CHST4 p.Arg118Gln Uncertain significance ★ ⚠ same type
CHST4 p.Arg130Gln Uncertain significance ★ ⚠ same type
CHST4 p.Arg130Trp 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/chst4-p-phe211cys (accessed [today's date]).

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