Is EMD p.Arg211Cys (c.631C>T) pathogenic?

EMD p.Arg211Cys (c.631C>T) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-10-20). AlphaMissense: likely benign (0.1274); Very rare (popmax 0.00295%, eas); Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Arg211Cys (c.631C>T)?

EMD p.Arg211Cys (c.631C>T) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Arg211Cys (c.631C>T) in the general population?

EMD p.Arg211Cys (c.631C>T) is very rare (popmax 0.00295%, eas) (gnomAD).

How is Emery-Dreifuss muscular dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EMD p.Arg211Cys (c.631C>T)?

AlphaMissense predicts likely benign (score 0.1274) — an in-silico prediction, not a clinical call.

EMD p.Arg211Cys

c.631C>T · rs782193940 · VCV1512845

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1274 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00295%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.1274	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -9.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.73, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	19.82	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00295% East Asian · 1/33,876 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000577% 7/1,212,396 alleles · very rare exomes 7/1,098,097 · genomes 0/114,299 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0042%	23,834
East Asiangrpmax	0.00295%	33,876
Admixed American	0.00217%	46,155
European (non-Finnish)	0.000335%	298,549

Remaining individuals 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.Arg211Cys
Coding: c.631C>T
MANE Select: NM_000117
dbSNP: rs782193940
Type: single nucleotide variant
Location: chrX:154381063 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 211: the 'interaction with f-actin' region

Full EMD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked Emery-Dreifuss muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Emery-Dreifuss muscular dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

EMD p.Arg211Gly Uncertain significance ★ ⚠ same residue
EMD p.Arg211His Conflicting classifications of pathogenicity ★ ⚠ same residue
EMD p.Arg211fs 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

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-arg211cys (accessed [today's date]).

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