Is EMD p.Thr165= (c.495G>A) pathogenic?

EMD p.Thr165= (c.495G>A) is classified Benign/Likely benign in EMD (ClinVar, Multiple submitters, 19 submitters; last evaluated 2026-02-03). Rare (popmax 0.158%, nfe); Associated with Emery-Dreifuss muscular dystrophy 1, X-linked.

What condition is associated with EMD p.Thr165= (c.495G>A)?

EMD p.Thr165= (c.495G>A) is associated with Emery-Dreifuss muscular dystrophy 1, X-linked, X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Thr165= (c.495G>A) in the general population?

EMD p.Thr165= (c.495G>A) is rare (popmax 0.158%, nfe) (gnomAD).

EMD p.Thr165=

c.495G>A · rs151074632 · VCV42276

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

gnomAD v4.1

Rare

rare (popmax 0.158%, nfe)

Conditions

Emery-Dreifuss muscular dystrophy 1, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.7	GERP -3.2
Overall
CADD	1.358	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.158% European (non-Finnish) · 1,411/895,086 alleles

Filtering AF 0.151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.148%

Overall 0.122% 1,471/1,209,810 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.158%	634
Remaining individualsnot grpmax-eligible	0.0714%	1,400
African / African-American	0.0262%	3,815
Middle Eastern	0.023%	4,355
South Asian	0.00879%	11,372
Admixed American	0.00654%	15,297
Finnishnot grpmax-eligible	0.00432%	23,167

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.Thr165=
Coding: c.495G>A
MANE Select: NM_000117
dbSNP: rs151074632
Type: single nucleotide variant
Location: chrX:154380927 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 165: the 'interaction with f-actin' region

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

Disease context

Emery-Dreifuss muscular dystrophy 1, X-linked — 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.Thr165Met 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-thr165 (accessed [today's date]).

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