Is EMD p.Asp72Val (c.215A>T) pathogenic?

EMD p.Asp72Val (c.215A>T) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-06-11). AlphaMissense: ambiguous (0.3479); Very rare (popmax 0.000894%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Asp72Val (c.215A>T)?

EMD p.Asp72Val (c.215A>T) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Asp72Val (c.215A>T) in the general population?

EMD p.Asp72Val (c.215A>T) is very rare (popmax 0.000894%, nfe) (gnomAD).

What do computational predictors say about EMD p.Asp72Val (c.215A>T)?

AlphaMissense predicts ambiguous (score 0.3479) — an in-silico prediction, not a clinical call.

EMD p.Asp72Val

c.215A>T · rs794729021 · VCV201783

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.3479 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000894%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3479	ambiguous
REVEL	0.732	pathogenic-leaning
SaProt	LLR -6.53	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.89 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.7	GERP 0.38, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	21.3	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 0.000894% European (non-Finnish) · 8/895,225 alleles

Filtering AF 0.000384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.00082% 9/1,097,912 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00214%	46,731
European (non-Finnish)grpmax	0.000894%	111,903

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp72Val
Coding: c.215A>T
MANE Select: NM_000117
dbSNP: rs794729021
Type: single nucleotide variant
Location: chrX:154379969 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 72: 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: X-linked Emery-Dreifuss muscular dystrophy Emery-Dreifuss muscular dystrophy

Similar variants

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
EMD c.450-2A>G Pathogenic/Likely 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-asp72val (accessed [today's date]).

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