Is CHST15 p.Ala437Val (c.1310C>T) pathogenic?

CHST15 p.Ala437Val (c.1310C>T) is classified Uncertain significance in CHST15 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: ambiguous (0.3412); Very rare (popmax 0.00667%, amr).

How common is CHST15 p.Ala437Val (c.1310C>T) in the general population?

CHST15 p.Ala437Val (c.1310C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about CHST15 p.Ala437Val (c.1310C>T)?

AlphaMissense predicts ambiguous (score 0.3412) — an in-silico prediction, not a clinical call.

CHST15 p.Ala437Val

c.1310C>T · rs755974129 · VCV2225139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3412 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Computational evidence

Protein change
AlphaMissense	0.3412	ambiguous
REVEL	0.365	indeterminate
SaProt	LLR -7.00	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 34 kb · p 1.6e-06 · regional, not allelic
Overall
CADD	28.8	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 0.00667% Admixed American · 4/59,948 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00062% 10/1,613,322 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,987
Remaining individualsnot grpmax-eligible	0.0016%	62,450
European (non-Finnish)	0.000424%	235,963

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.Ala437Val
Coding: c.1310C>T
MANE Select: NM_001270764
dbSNP: rs755974129
Type: single nucleotide variant
Location: chr10:124021293 (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.Ala437Ser 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-ala437val (accessed [today's date]).

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