Is DEXI p.Leu73Phe (c.217C>T) pathogenic?

DEXI p.Leu73Phe (c.217C>T) is classified Uncertain significance in DEXI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-19). AlphaMissense: ambiguous (0.4859); Very rare (popmax 0.00407%, nfe).

How common is DEXI p.Leu73Phe (c.217C>T) in the general population?

DEXI p.Leu73Phe (c.217C>T) is very rare (popmax 0.00407%, nfe) (gnomAD).

What do computational predictors say about DEXI p.Leu73Phe (c.217C>T)?

AlphaMissense predicts ambiguous (score 0.4859) — an in-silico prediction, not a clinical call.

DEXI p.Leu73Phe

c.217C>T · rs770699316 · VCV2314139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4859	ambiguous
REVEL	0.362	indeterminate
SaProt	LLR -6.94	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 284 bp · p 0.051 · regional, not allelic
Overall
CADD	32.0	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 0.00407% European (non-Finnish) · 48/1,179,870 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.0031% 50/1,613,628 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00407%	24,581
African / African-American	0.00267%	37,468

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.Leu73Phe
Coding: c.217C>T
MANE Select: NM_000246 · reported on NM_014015
dbSNP: rs770699316
Type: single nucleotide variant
Location: chr16:10941789 (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-leu73phe (accessed [today's date]).

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