Is EMD p.Asp6Glu (c.18T>A) pathogenic?

EMD p.Asp6Glu (c.18T>A) is classified Uncertain significance in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-08). AlphaMissense: likely benign (0.1585); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Asp6Glu (c.18T>A)?

EMD p.Asp6Glu (c.18T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is EMD p.Asp6Glu (c.18T>A) in the general population?

EMD p.Asp6Glu (c.18T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMD p.Asp6Glu (c.18T>A)?

AlphaMissense predicts likely benign (score 0.1585) — an in-silico prediction, not a clinical call.

EMD p.Asp6Glu

c.18T>A · rs2522786991 · VCV1782290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1585 · 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	0.1585	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.77	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 -0.68	GERP -1.9
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	6.781	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.Asp6Glu
Coding: c.18T>A
MANE Select: NM_000117
dbSNP: rs2522786991
Type: single nucleotide variant
Location: chrX:154379502 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 6: the lem domain; an α-helix

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-asp6glu (accessed [today's date]).

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