Is EMD p.Thr43= (c.129C>T) pathogenic?

EMD p.Thr43= (c.129C>T) is classified Likely benign in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-14). Ultra-rare (popmax 0.0296%, eas); Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Thr43= (c.129C>T)?

EMD p.Thr43= (c.129C>T) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Thr43= (c.129C>T) in the general population?

EMD p.Thr43= (c.129C>T) is ultra-rare (popmax 0.0296%, eas) (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.Thr43=

c.129C>T · rs781938390 · VCV1143199

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, eas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP 0.071, phastCons 0.99
Overall
CADD	12.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0296% East Asian · 10/33,738 alleles

Filtering AF 0.016% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00124% 15/1,207,229 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0296%	3,374
Middle Eastern	0.0231%	4,336
Remaining individualsnot grpmax-eligible	0.00211%	47,493
European (non-Finnish)	0.000335%	298,126

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.Thr43=
Coding: c.129C>T
MANE Select: NM_000117
dbSNP: rs781938390
Type: single nucleotide variant
Location: chrX:154379736 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 43: the lem domain; an α-helix

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.Thr43Ile Uncertain significance ★ ⚠ same residue
EMD p.Thr43Ser 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-thr43 (accessed [today's date]).

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