Is EMD p.Ser143Phe (c.428C>T) pathogenic?

EMD p.Ser143Phe (c.428C>T) is classified Conflicting classifications of pathogenicity in EMD (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-01-17). AlphaMissense: likely benign (0.1679); Rare (popmax 0.138%, mid); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Ser143Phe (c.428C>T)?

EMD p.Ser143Phe (c.428C>T) is associated with Cardiovascular phenotype, cardiomyopathy, X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Ser143Phe (c.428C>T) in the general population?

EMD p.Ser143Phe (c.428C>T) is rare (popmax 0.138%, mid) (gnomAD).

What do computational predictors say about EMD p.Ser143Phe (c.428C>T)?

AlphaMissense predicts likely benign (score 0.1679) — an in-silico prediction, not a clinical call.

EMD p.Ser143Phe

c.428C>T · rs139983160 · VCV237013

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.1679 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.138%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1679	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -8.46	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 1.5	GERP 1.5, phastCons 0.044
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	19.29	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 0.138% Middle Eastern · 6/4,338 alleles

Filtering AF 0.0601% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0411%

Overall 0.0183% 222/1,210,717 alleles · rare exomes 198/1,098,085 · genomes 24/112,632 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.48%	68
Middle Easterngrpmax	0.138%	723
European (non-Finnish)	0.0213%	4,687
Remaining individualsnot grpmax-eligible	0.0147%	6,804
South Asian	0.00879%	11,376
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,036
Admixed American	0.00435%	22,990

Amish 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.Ser143Phe
Coding: c.428C>T
MANE Select: NM_000117
dbSNP: rs139983160
Type: single nucleotide variant
Location: chrX:154380781 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 143: 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

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.Ser143del Uncertain significance ★★ 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-ser143phe (accessed [today's date]).

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