Is CHST2 p.Ala55Thr (c.163G>A) pathogenic?

CHST2 p.Ala55Thr (c.163G>A) is classified Uncertain significance in CHST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). AlphaMissense: likely benign (0.2613); Very rare (popmax 0.000523%, nfe).

How common is CHST2 p.Ala55Thr (c.163G>A) in the general population?

CHST2 p.Ala55Thr (c.163G>A) is very rare (popmax 0.000523%, nfe) (gnomAD).

What do computational predictors say about CHST2 p.Ala55Thr (c.163G>A)?

AlphaMissense predicts likely benign (score 0.2613) — an in-silico prediction, not a clinical call.

CHST2 p.Ala55Thr

c.163G>A · VCV3267229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000523%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2613	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 481 bp · p 0.0045 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000523% European (non-Finnish) · 6/1,146,474 alleles

Filtering AF 0.000188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000124%

Overall 0.000431% 6/1,391,950 alleles · very rare

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: CHST2
Protein: p.Ala55Thr
Coding: c.163G>A
MANE Select: NM_004267
Type: single nucleotide variant
Location: chr3:143120979 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.61

Full CHST2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST2 p.Ala116Pro Uncertain significance ★ ⚠ same type
CHST2 p.Ala116Ser Uncertain significance ★ ⚠ same type
CHST2 p.Ala118Gly Uncertain significance ★ ⚠ same type
CHST2 p.Ala131Val Uncertain significance ★ ⚠ same type
CHST2 p.Ala24Val Uncertain significance ★ ⚠ same type
CHST2 p.Ala25Thr Uncertain significance ★ ⚠ same type
CHST2 p.Ala387Gly Uncertain significance ★ ⚠ same type
CHST2 p.Ala455Val 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/chst2-p-ala55thr (accessed [today's date]).

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