Is DEXI p.Pro15Ser (c.43C>T) pathogenic?

DEXI p.Pro15Ser (c.43C>T) is classified Uncertain significance in DEXI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). AlphaMissense: likely benign (0.0872); Very rare (popmax 8.67e-05%, nfe).

How common is DEXI p.Pro15Ser (c.43C>T) in the general population?

DEXI p.Pro15Ser (c.43C>T) is very rare (popmax 8.67e-05%, nfe) (gnomAD).

What do computational predictors say about DEXI p.Pro15Ser (c.43C>T)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

DEXI p.Pro15Ser

c.43C>T · rs2544776926 · VCV2544596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.67e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.4	GERP 0.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 284 bp · p 0.051 · regional, not allelic
Overall
CADD	21.9	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 8.67e-05% European (non-Finnish) · 1/1,153,820 alleles

Overall 7.1e-05% 1/1,408,358 alleles · very rare

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: DEXI
Protein: p.Pro15Ser
Coding: c.43C>T
MANE Select: NM_000246 · reported on NM_014015
dbSNP: rs2544776926
Type: single nucleotide variant
Location: chr16:10941963 (GRCh38)

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

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/dexi-p-pro15ser (accessed [today's date]).

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