Is EMD p.Thr101Ser (c.302C>G) pathogenic?

EMD p.Thr101Ser (c.302C>G) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-16). AlphaMissense: likely benign (0.101); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Thr101Ser (c.302C>G)?

EMD p.Thr101Ser (c.302C>G) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Thr101Ser (c.302C>G) in the general population?

EMD p.Thr101Ser (c.302C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMD p.Thr101Ser (c.302C>G)?

AlphaMissense predicts likely benign (score 0.101) — an in-silico prediction, not a clinical call.

EMD p.Thr101Ser

c.302C>G · rs1023451135 · VCV1799010

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.101 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.101	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -5.17	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 -0.15	GERP -2.8, phastCons 0.01
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	3.591	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EMD
Protein: p.Thr101Ser
Coding: c.302C>G
MANE Select: NM_000117
dbSNP: rs1023451135
Type: single nucleotide variant
Location: chrX:154380270 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 101: 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

Similar variants

EMD p.Thr101= Likely benign ★ same residue
EMD p.Thr101Ile 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

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-thr101ser (accessed [today's date]).

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