Is EMD p.Ile164= (c.492C>T) pathogenic?

EMD p.Ile164= (c.492C>T) is classified Likely benign in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-14). Very rare (popmax 0.00175%, afr); Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Ile164= (c.492C>T)?

EMD p.Ile164= (c.492C>T) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Ile164= (c.492C>T) in the general population?

EMD p.Ile164= (c.492C>T) is very rare (popmax 0.00175%, afr) (gnomAD).

How is Emery-Dreifuss muscular dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EMD p.Ile164=

c.492C>T · rs1286873712 · VCV1083995

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.25	GERP -3.2, phastCons 0.28
Overall
CADD	2.326	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% African / African-American · 1/57,227 alleles

Overall 0.000892% 1/112,058 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.Ile164=
Coding: c.492C>T
MANE Select: NM_000117
dbSNP: rs1286873712
Type: single nucleotide variant
Location: chrX:154380924 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 164: the 'interaction with f-actin' region

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

Disease context

X-linked Emery-Dreifuss muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Emery-Dreifuss muscular dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

EMD p.Ile164Leu Uncertain significance ★★ ⚠ same residue
EMD p.Ile164Val 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

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-ile164 (accessed [today's date]).

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