Is EMD p.Ser49= (c.147G>T) pathogenic?

EMD p.Ser49= (c.147G>T) is classified Likely benign in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-12). Very rare (popmax 0.00175%, afr); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Ser49= (c.147G>T)?

EMD p.Ser49= (c.147G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is EMD p.Ser49= (c.147G>T) in the general population?

EMD p.Ser49= (c.147G>T) is very rare (popmax 0.00175%, afr) (gnomAD).

EMD p.Ser49=

c.147G>T · rs2067875354 · VCV1773544

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -2.4
Overall
CADD	8.002	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% African / African-American · 1/56,983 alleles

Overall 8.3e-05% 1/1,205,318 alleles · very rare exomes 0/1,093,698 · genomes 1/111,620 · joint denominator

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.Ser49=
Coding: c.147G>T
MANE Select: NM_000117
dbSNP: rs2067875354
Type: single nucleotide variant
Location: chrX:154379754 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 49: the 'interaction with f-actin' region; a modified residue (phosphoserine; by pka)

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

Similar variants

EMD c.400-3C>T Uncertain significance ★★ same condition
EMD c.449+4C>T Uncertain significance ★★ same condition
EMD p.Arg168Cys Uncertain significance ★★ ⚠ same condition
EMD p.Arg203His Uncertain significance ★★ ⚠ same condition
EMD p.Arg207Gln Uncertain significance ★★ ⚠ same condition
EMD p.Asp72Val Uncertain significance ★★ ⚠ same condition
EMD p.Glu146Lys Uncertain significance ★★ ⚠ same condition
EMD p.Gly24Arg Uncertain significance ★★ ⚠ 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-ser49 (accessed [today's date]).

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