Is EMD p.Val238Ile (c.712G>A) pathogenic?

EMD p.Val238Ile (c.712G>A) is classified Conflicting classifications of pathogenicity in EMD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-10). AlphaMissense: likely benign (0.0901); Very rare (popmax 0.00217%, amr); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Val238Ile (c.712G>A)?

EMD p.Val238Ile (c.712G>A) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Val238Ile (c.712G>A) in the general population?

EMD p.Val238Ile (c.712G>A) is very rare (popmax 0.00217%, amr) (gnomAD).

What do computational predictors say about EMD p.Val238Ile (c.712G>A)?

AlphaMissense predicts likely benign (score 0.0901) — an in-silico prediction, not a clinical call.

EMD p.Val238Ile

c.712G>A · rs782455914 · VCV837439

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0901 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0901	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -0.62, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	9.983	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 0.00217% Admixed American · 1/46,005 alleles

Filtering AF 0.000565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000412%

Overall 0.001% 11/1,097,992 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00217%	46,005
European (non-Finnish)	0.00112%	89,541

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.Val238Ile
Coding: c.712G>A
MANE Select: NM_000117
dbSNP: rs782455914
Type: single nucleotide variant
Location: chrX:154381144 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB

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.Val238= 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-val238ile (accessed [today's date]).

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