Is CHST15 p.Val219Ala (c.656T>C) pathogenic?

CHST15 p.Val219Ala (c.656T>C) is classified Uncertain significance in CHST15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.0962); Rare (popmax 0.1%, mid).

How common is CHST15 p.Val219Ala (c.656T>C) in the general population?

CHST15 p.Val219Ala (c.656T>C) is rare (popmax 0.1%, mid) (gnomAD).

What do computational predictors say about CHST15 p.Val219Ala (c.656T>C)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

CHST15 p.Val219Ala

c.656T>C · rs199953738 · VCV2569334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.1%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -4.43	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 2.4	GERP -1.3, phastCons 0.95
Regional constraint	o/e 1.37	unconstrained · MANE · 246 bp · p 5.2e-05 · regional, not allelic
Overall
CADD	12.18	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 0.1% Middle Eastern · 6/5,972 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.00495% 79/1,594,594 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.1%	995
Remaining individualsnot grpmax-eligible	0.0227%	4,400
South Asian	0.00673%	14,865
East Asian	0.00455%	21,970
European (non-Finnish)	0.00411%	24,341
Ashkenazi Jewishnot grpmax-eligible	0.00348%	28,728
Admixed American	0.00345%	28,997

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: CHST15
Protein: p.Val219Ala
Coding: c.656T>C
MANE Select: NM_001270764
dbSNP: rs199953738
Type: single nucleotide variant
Location: chr10:124044810 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.20

Full CHST15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST15 p.Val219Met Uncertain significance ★ ⚠ same residue
CHST15 p.Ala16Thr Benign ★★ same type
CHST15 p.Arg224= Benign ★★ same type
CHST15 p.Ala241Val Uncertain significance ★ ⚠ same type
CHST15 p.Ala283Ser Uncertain significance ★ ⚠ same type
CHST15 p.Ala321Thr Uncertain significance ★ ⚠ same type
CHST15 p.Ala330Ser Uncertain significance ★ ⚠ same type
CHST15 p.Ala357Ser 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/chst15-p-val219ala (accessed [today's date]).

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