Is EMD p.Ser141Phe (c.422C>T) pathogenic?

EMD p.Ser141Phe (c.422C>T) is classified Conflicting classifications of pathogenicity in EMD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1397); Very rare (popmax 0.00523%, afr); Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Ser141Phe (c.422C>T)?

EMD p.Ser141Phe (c.422C>T) is associated with X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy 1, X-linked (ClinVar).

How common is EMD p.Ser141Phe (c.422C>T) in the general population?

EMD p.Ser141Phe (c.422C>T) is very rare (popmax 0.00523%, afr) (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.Ser141Phe (c.422C>T)?

AlphaMissense predicts likely benign (score 0.1397) — an in-silico prediction, not a clinical call.

EMD p.Ser141Phe

c.422C>T · rs1262954618 · VCV1495732

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1397 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00523%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.1397	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -7.43	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 2	GERP 1, phastCons 0.98
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	20.3	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 0.00523% African / African-American · 3/57,384 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000685%

Overall 0.000826% 10/1,210,560 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00523%	19,128
Admixed American	0.00218%	45,952
European (non-Finnish)	0.00067%	149,211

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.Ser141Phe
Coding: c.422C>T
MANE Select: NM_000117
dbSNP: rs1262954618
Type: single nucleotide variant
Location: chrX:154380775 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 141: a modified residue (phosphoserine); 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

Also linked: Emery-Dreifuss muscular dystrophy 1, X-linked

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.Ser141= 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-ser141phe (accessed [today's date]).

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