Is EMD p.Leu7Phe (c.19C>T) pathogenic?

EMD p.Leu7Phe (c.19C>T) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-05-13). AlphaMissense: ambiguous (0.397); Very rare (popmax 0.00253%, amr); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Leu7Phe (c.19C>T)?

EMD p.Leu7Phe (c.19C>T) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Leu7Phe (c.19C>T) in the general population?

EMD p.Leu7Phe (c.19C>T) is very rare (popmax 0.00253%, amr) (gnomAD).

What do computational predictors say about EMD p.Leu7Phe (c.19C>T)?

AlphaMissense predicts ambiguous (score 0.397) — an in-silico prediction, not a clinical call.

EMD p.Leu7Phe

c.19C>T · rs2067873080 · VCV978372

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.397 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00253%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.397	ambiguous
REVEL	0.344	indeterminate
SaProt	LLR -9.31	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.29, phastCons 0.83
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	18.85	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 0.00253% Admixed American · 1/39,568 alleles

Filtering AF 3.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000284% 3/1,055,332 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00253%	39,568
European (non-Finnish)	0.000229%	436,990

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: EMD
Protein: p.Leu7Phe
Coding: c.19C>T
MANE Select: NM_000117
dbSNP: rs2067873080
Type: single nucleotide variant
Location: chrX:154379503 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 7: the lem domain

Full EMD 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

Also linked: X-linked Emery-Dreifuss muscular dystrophy

Similar variants

EMD p.Leu7His Uncertain significance ★★ ⚠ same residue
EMD c.187+1G>A Pathogenic ★★ same condition
EMD c.187+1G>T Pathogenic/Likely pathogenic ★★ same condition
EMD c.265+1G>A Likely pathogenic ★★ same condition
EMD c.266-2A>G Pathogenic ★★ same condition
EMD c.266-3A>G Pathogenic ★★ same condition
EMD c.399+1G>T Pathogenic ★★ same condition
EMD c.399+2T>C Pathogenic ★★ 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/emd-p-leu7phe (accessed [today's date]).

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