Is EMD p.Met191Thr (c.572T>C) pathogenic?

EMD p.Met191Thr (c.572T>C) is classified Likely benign in EMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-12). AlphaMissense: likely benign (0.0778); Very rare (popmax 0.00279%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Met191Thr (c.572T>C)?

EMD p.Met191Thr (c.572T>C) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Met191Thr (c.572T>C) in the general population?

EMD p.Met191Thr (c.572T>C) is very rare (popmax 0.00279%, nfe) (gnomAD).

What do computational predictors say about EMD p.Met191Thr (c.572T>C)?

AlphaMissense predicts likely benign (score 0.0778) — an in-silico prediction, not a clinical call.

EMD p.Met191Thr

c.572T>C · rs782244432 · VCV1011317

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0778 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00279%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0778	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -4.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.80 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.063	GERP -2.3, phastCons 0.002
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	0.442	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 0.00279% European (non-Finnish) · 25/895,181 alleles

Filtering AF 0.00192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00207% 25/1,210,243 alleles · very rare

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.Met191Thr
Coding: c.572T>C
MANE Select: NM_000117
dbSNP: rs782244432
Type: single nucleotide variant
Location: chrX:154381004 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 191: 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.Met191Val Conflicting classifications of pathogenicity ★ ⚠ same residue
EMD p.Met191fs 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
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-met191thr (accessed [today's date]).

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