Is EMD p.Tyr4= (c.12C>T) pathogenic?

EMD p.Tyr4= (c.12C>T) is classified Conflicting classifications of pathogenicity in EMD (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0142%, afr); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Tyr4= (c.12C>T)?

EMD p.Tyr4= (c.12C>T) is associated with Cardiovascular phenotype, cardiomyopathy, X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Tyr4= (c.12C>T) in the general population?

EMD p.Tyr4= (c.12C>T) is ultra-rare (popmax 0.0142%, afr) (gnomAD).

EMD p.Tyr4=

c.12C>T · rs782011714 · VCV290626

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0142%, afr)

Conditions

Cardiovascular phenotype

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 1.3	GERP 1.4, phastCons 0.99
Overall
CADD	8.917	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0142% African / African-American · 8/56,300 alleles

Filtering AF 0.00699% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00509%

Overall 0.00437% 51/1,168,059 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0142%	7,037
European (non-Finnish)	0.00469%	21,300
Remaining individualsnot grpmax-eligible	0.00436%	22,952

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.Tyr4=
Coding: c.12C>T
MANE Select: NM_000117
dbSNP: rs782011714
Type: single nucleotide variant
Location: chrX:154379496 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 4: the lem domain; an α-helix

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: cardiomyopathy X-linked Emery-Dreifuss muscular dystrophy Emery-Dreifuss muscular dystrophy

Similar variants

EMD p.Tyr4Ter Pathogenic ★ 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-tyr4 (accessed [today's date]).

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