Is CHST15 p.Val83Ile (c.247G>A) pathogenic?

CHST15 p.Val83Ile (c.247G>A) is classified Uncertain significance in CHST15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely benign (0.0672); Rare (popmax 0.303%, afr).

How common is CHST15 p.Val83Ile (c.247G>A) in the general population?

CHST15 p.Val83Ile (c.247G>A) is rare (popmax 0.303%, afr) (gnomAD).

What do computational predictors say about CHST15 p.Val83Ile (c.247G>A)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

CHST15 p.Val83Ile

c.247G>A · VCV4653654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.303%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -5.65	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 -3.4
Regional constraint	o/e 0.74	unconstrained · MANE · 1,346 bp · p 4.5e-05 · regional, not allelic
Overall
CADD	8.683	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 0.303% African / African-American · 227/75,018 alleles

Filtering AF 0.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.258%

Overall 0.0215% 347/1,614,140 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.303%	330
Remaining individualsnot grpmax-eligible	0.024%	4,167
European (non-Finnish)	0.00847%	11,800
Admixed American	0.00833%	12,004

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.Val83Ile
Coding: c.247G>A
MANE Select: NM_001270764
Type: single nucleotide variant
Location: chr10:124045966 (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.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
CHST15 p.Ala412Thr 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-val83ile (accessed [today's date]).

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