Is EMD p.Arg204Ser (c.610C>A) pathogenic?

EMD p.Arg204Ser (c.610C>A) is classified Uncertain significance in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-09). AlphaMissense: likely pathogenic (0.6325); Very rare (popmax 8.25e-05%); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Arg204Ser (c.610C>A)?

EMD p.Arg204Ser (c.610C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is EMD p.Arg204Ser (c.610C>A) in the general population?

EMD p.Arg204Ser (c.610C>A) is very rare (popmax 8.25e-05%) (gnomAD).

What do computational predictors say about EMD p.Arg204Ser (c.610C>A)?

AlphaMissense predicts likely pathogenic (score 0.6325) — an in-silico prediction, not a clinical call.

EMD p.Arg204Ser

c.610C>A · VCV4870387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6325 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.25e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.6325	likely pathogenic
REVEL	0.228	benign-leaning
SaProt	LLR -6.36	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 1.6, phastCons 0.99
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	21.0	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 8.25e-05%

Overall 8.25e-05% 1/1,212,179 alleles · very rare exomes 1/1,098,070 · genomes 0/114,109 · 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.Arg204Ser
Coding: c.610C>A
MANE Select: NM_000117
Type: single nucleotide variant
Location: chrX:154381042 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 204: 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

Similar variants

EMD p.Arg204Gly Conflicting classifications of pathogenicity ★ same residue
EMD p.Arg204His Conflicting classifications of pathogenicity ★ ⚠ same residue
EMD p.Arg204Cys Uncertain significance ★★ ⚠ same residue
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

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-arg204ser (accessed [today's date]).

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