Is EMD p.Asp149His (c.445G>C) pathogenic?

EMD p.Asp149His (c.445G>C) is classified Benign/Likely benign in EMD (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.2483); Rare (popmax 0.53%, eas); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Asp149His (c.445G>C)?

EMD p.Asp149His (c.445G>C) is associated with Cardiovascular phenotype, cardiomyopathy, X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Asp149His (c.445G>C) in the general population?

EMD p.Asp149His (c.445G>C) is rare (popmax 0.53%, eas) (gnomAD).

What do computational predictors say about EMD p.Asp149His (c.445G>C)?

AlphaMissense predicts likely benign (score 0.2483) — an in-silico prediction, not a clinical call.

EMD p.Asp149His

c.445G>C · rs2070818 · VCV237014

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.2483 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.53%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2483	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.4	GERP 0.44, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	21.1	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 0.53% East Asian · 179/33,764 alleles

Filtering AF 0.467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.442%

Overall 0.0177% 214/1,210,652 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.53%	189
South Asian	0.0387%	2,585
Remaining individualsnot grpmax-eligible	0.0147%	6,803
Admixed American	0.00435%	22,989
African / African-American	0.00174%	57,411
European (non-Finnish)	0.000335%	298,427

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.Asp149His
Coding: c.445G>C
MANE Select: NM_000117
dbSNP: rs2070818
Type: single nucleotide variant
Location: chrX:154380798 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 149: a UniProt-annotated variant site (in); 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 Emery-Dreifuss muscular dystrophy

Similar variants

EMD p.Asp149= 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-asp149his (accessed [today's date]).

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