Is EMD p.Lys88Asn (c.264G>C) pathogenic?

EMD p.Lys88Asn (c.264G>C) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-29). AlphaMissense: ambiguous (0.54); Very rare (popmax 0.000671%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Lys88Asn (c.264G>C)?

EMD p.Lys88Asn (c.264G>C) is associated with Cardiovascular phenotype, cardiomyopathy, X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Lys88Asn (c.264G>C) in the general population?

EMD p.Lys88Asn (c.264G>C) is very rare (popmax 0.000671%, nfe) (gnomAD).

What do computational predictors say about EMD p.Lys88Asn (c.264G>C)?

AlphaMissense predicts ambiguous (score 0.54) — an in-silico prediction, not a clinical call.

EMD p.Lys88Asn

c.264G>C · rs782178894 · VCV1794316

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.54 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000671%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.54	ambiguous
REVEL	0.252	benign-leaning
SaProt	LLR -5.52	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 1.4, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	22.7	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

Grpmax group 0.000671% European (non-Finnish) · 6/894,237 alleles

Filtering AF 0.000241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 6/1,209,417 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.Lys88Asn
Coding: c.264G>C
MANE Select: NM_000117
dbSNP: rs782178894
Type: single nucleotide variant
Location: chrX:154380018 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 88: the 'interaction with f-actin' 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: cardiomyopathy X-linked Emery-Dreifuss muscular dystrophy

Similar variants

EMD p.Lys88Ter Pathogenic ★ 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-lys88asn (accessed [today's date]).

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