Is EMD p.Pro22Leu (c.65C>T) pathogenic?

EMD p.Pro22Leu (c.65C>T) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-22). AlphaMissense: likely pathogenic (0.6348); Absent from gnomAD v4.1; Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Pro22Leu (c.65C>T)?

EMD p.Pro22Leu (c.65C>T) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Pro22Leu (c.65C>T) in the general population?

EMD p.Pro22Leu (c.65C>T) is absent from gnomAD v4.1 (gnomAD).

How is Emery-Dreifuss muscular dystrophy inherited?

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

What do computational predictors say about EMD p.Pro22Leu (c.65C>T)?

AlphaMissense predicts likely pathogenic (score 0.6348) — an in-silico prediction, not a clinical call.

EMD p.Pro22Leu

c.65C>T · rs794729017 · VCV201779

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6348 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,170,516)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.6348	likely pathogenic
REVEL	0.248	benign-leaning
SaProt	LLR -12.51	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	25.7	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

No allele count reported in gnomAD v4.1 (AN 1,170,516). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EMD
Protein: p.Pro22Leu
Coding: c.65C>T
MANE Select: NM_000117
dbSNP: rs794729017
Type: single nucleotide variant
Location: chrX:154379549 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 22: the lem domain

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.Pro22= Likely benign ★ 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-pro22leu (accessed [today's date]).

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