Is EMB p.Leu19= (c.57C>T) pathogenic?

EMB p.Leu19= (c.57C>T) is classified Likely benign in EMB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-11). Ultra-rare (popmax 0.0216%, mid).

How common is EMB p.Leu19= (c.57C>T) in the general population?

EMB p.Leu19= (c.57C>T) is ultra-rare (popmax 0.0216%, mid) (gnomAD).

EMB p.Leu19=

c.57C>T · rs1579749665 · VCV732404

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0216%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP -0.6
Overall
CADD	6.144	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0216% Middle Eastern · 1/4,636 alleles

Overall 0.000657% 1/152,258 alleles · ultra-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: EMB
Protein: p.Leu19=
Coding: c.57C>T
MANE Select: NM_003400 · reported on NM_198449
dbSNP: rs1579749665
Type: single nucleotide variant
Location: chr5:50441095 (GRCh38)
Structure: AlphaFold pLDDT 91.62 · 19 PDB
Residue 19: the 'necessary for htlv-1 rex-mediated mrna export' region; a β-strand

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

Similar variants

XPO1 c.888+9A>G Benign ★★ same type
XPO1 p.Arg305= Benign ★★ same type
XPO1 p.Leu625= Likely benign ★★ same type
XPO1 p.Lys757= Likely benign ★★ same type
XPO1 p.Thr846= Benign ★★ same type
XPO1 c.1887+1G>T Pathogenic ★ same type
XPO1 c.888+1G>A Pathogenic ★ same type
XPO1 p.Arg765Ter Pathogenic ★ 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/emb-p-leu19 (accessed [today's date]).

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