Is CHST2 p.Met70Val (c.208A>G) pathogenic?

CHST2 p.Met70Val (c.208A>G) is classified Uncertain significance in CHST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0818); Very rare (popmax 0.00648%, nfe).

How common is CHST2 p.Met70Val (c.208A>G) in the general population?

CHST2 p.Met70Val (c.208A>G) is very rare (popmax 0.00648%, nfe) (gnomAD).

What do computational predictors say about CHST2 p.Met70Val (c.208A>G)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

CHST2 p.Met70Val

c.208A>G · VCV4228609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00648%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.462	indeterminate
SaProt	LLR -3.79	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 7.3	phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 481 bp · p 0.0045 · regional, not allelic
Overall
CADD	20.8	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 0.00648% European (non-Finnish) · 74/1,141,712 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00484%

Overall 0.00488% 75/1,535,538 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00648%	15,429
Remaining individualsnot grpmax-eligible	0.00169%	59,322

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.Met70Val
Coding: c.208A>G
MANE Select: NM_004267
Type: single nucleotide variant
Location: chr3:143121024 (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-met70val (accessed [today's date]).

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