Is CHST14 p.Ser43Pro (c.127T>C) pathogenic?

CHST14 p.Ser43Pro (c.127T>C) is classified Uncertain significance in CHST14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-19). AlphaMissense: likely benign (0.2823); Very rare (popmax 0.00409%, afr); Associated with Cardiovascular phenotype.

What condition is associated with CHST14 p.Ser43Pro (c.127T>C)?

CHST14 p.Ser43Pro (c.127T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is CHST14 p.Ser43Pro (c.127T>C) in the general population?

CHST14 p.Ser43Pro (c.127T>C) is very rare (popmax 0.00409%, afr) (gnomAD).

What do computational predictors say about CHST14 p.Ser43Pro (c.127T>C)?

AlphaMissense predicts likely benign (score 0.2823) — an in-silico prediction, not a clinical call.

CHST14 p.Ser43Pro

c.127T>C · rs1473645945 · VCV3229031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00409%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2823	likely benign
REVEL	0.466	indeterminate
SaProt	LLR -4.51	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 7.8	GERP 0.24, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,127 bp · p 0.038 · regional, not allelic
Overall
CADD	26.9	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 0.00409% African / African-American · 3/73,376 alleles

Filtering AF 0.00109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000501%

Overall 0.000194% 3/1,546,310 alleles · very rare exomes 2/1,394,298 · genomes 1/152,012 · joint denominator

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: CHST14
Protein: p.Ser43Pro
Coding: c.127T>C
MANE Select: NM_130468
dbSNP: rs1473645945
Type: single nucleotide variant
Location: chr15:40471340 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.17

Full CHST14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHST14 p.Ser43Phe Uncertain significance ★ ⚠ same residue
CHST14 p.Ser43= Likely benign ★ same residue
CHST14 p.Arg320Ter Likely pathogenic ★★ same condition
CHST14 p.Ala100Thr Uncertain significance ★★ ⚠ same condition
CHST14 p.Ala15Pro Uncertain significance ★★ ⚠ same condition
CHST14 p.Ala346Pro Uncertain significance ★★ ⚠ same condition
CHST14 p.Ala373Ser Uncertain significance ★★ ⚠ same condition
CHST14 p.Ala373Val Uncertain significance ★★ ⚠ same condition

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/chst14-p-ser43pro (accessed [today's date]).

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