Is EMD p.Gly156Ser (c.466G>A) pathogenic?

EMD p.Gly156Ser (c.466G>A) is classified Benign/Likely benign in EMD (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0784); Rare (popmax 0.286%, afr); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Gly156Ser (c.466G>A)?

EMD p.Gly156Ser (c.466G>A) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Gly156Ser (c.466G>A) in the general population?

EMD p.Gly156Ser (c.466G>A) is rare (popmax 0.286%, afr) (gnomAD).

What do computational predictors say about EMD p.Gly156Ser (c.466G>A)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

EMD p.Gly156Ser

c.466G>A · rs144594695 · VCV201771

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.286%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -4.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 1.7	GERP 0.45, phastCons 0.95
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	17.9	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 0.286% African / African-American · 164/57,368 alleles

Filtering AF 0.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.236%

Overall 0.0155% 188/1,210,355 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.286%	350
Remaining individualsnot grpmax-eligible	0.0084%	11,906
Admixed American	0.00653%	15,318
European (non-Finnish)	0.0019%	52,660

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.Gly156Ser
Coding: c.466G>A
MANE Select: NM_000117
dbSNP: rs144594695
Type: single nucleotide variant
Location: chrX:154380898 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 156: 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 p.Gly156Arg 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
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-gly156ser (accessed [today's date]).

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