Is EMD p.Leu179= (c.535C>T) pathogenic?

EMD p.Leu179= (c.535C>T) is classified Likely benign in EMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-03). Very rare (popmax 0.000447%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Leu179= (c.535C>T)?

EMD p.Leu179= (c.535C>T) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Leu179= (c.535C>T) in the general population?

EMD p.Leu179= (c.535C>T) is very rare (popmax 0.000447%, nfe) (gnomAD).

EMD p.Leu179=

c.535C>T · rs1260147167 · VCV1640433

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

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 -0.94	GERP -3.2
Overall
CADD	1.322	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000447% European (non-Finnish) · 4/895,457 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000364% 4/1,097,922 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: EMD
Protein: p.Leu179=
Coding: c.535C>T
MANE Select: NM_000117
dbSNP: rs1260147167
Type: single nucleotide variant
Location: chrX:154380967 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 179: the 'interaction with f-actin' region; the 'interaction with ctnnb1' region

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 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
EMD c.450-2A>G Pathogenic/Likely 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-leu179 (accessed [today's date]).

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