Is EMD p.Lys37Met (c.110A>T) pathogenic?

EMD p.Lys37Met (c.110A>T) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-31). AlphaMissense: likely pathogenic (0.7062); Very rare (popmax 0.00349%, afr); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Lys37Met (c.110A>T)?

EMD p.Lys37Met (c.110A>T) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Lys37Met (c.110A>T) in the general population?

EMD p.Lys37Met (c.110A>T) is very rare (popmax 0.00349%, afr) (gnomAD).

What do computational predictors say about EMD p.Lys37Met (c.110A>T)?

AlphaMissense predicts likely pathogenic (score 0.7062) — an in-silico prediction, not a clinical call.

EMD p.Lys37Met

c.110A>T · rs1085307681 · VCV426553

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7062 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00349%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7062	likely pathogenic · top 10% in EMD
REVEL	0.469	indeterminate
SaProt	LLR -13.55	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00349% African / African-American · 2/57,228 alleles

Filtering AF 0.00058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000217%

Overall 0.000497% 6/1,208,215 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00349%	28,614
European (non-Finnish)	0.000447%	223,659

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.Lys37Met
Coding: c.110A>T
MANE Select: NM_000117
dbSNP: rs1085307681
Type: single nucleotide variant
Location: chrX:154379717 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 37: the lem domain; a UniProt-annotated variant site (in cmd3c; likely pathogenic; loss of nuclear localization); 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: X-linked Emery-Dreifuss muscular dystrophy Emery-Dreifuss muscular dystrophy

Similar variants

EMD p.Lys37Arg Uncertain significance ★ ⚠ same residue
EMD p.Lys37Ile Uncertain significance ★★ same residue
EMD p.Lys37del Conflicting classifications of pathogenicity ★ 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

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-lys37met (accessed [today's date]).

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