Is EMD p.Arg17Pro (c.50G>C) pathogenic?

EMD p.Arg17Pro (c.50G>C) is classified Uncertain significance in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-20). AlphaMissense: likely pathogenic (0.9416); Absent from gnomAD v4.1.

How common is EMD p.Arg17Pro (c.50G>C) in the general population?

EMD p.Arg17Pro (c.50G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMD p.Arg17Pro (c.50G>C)?

AlphaMissense predicts likely pathogenic (score 0.9416) — an in-silico prediction, not a clinical call.

EMD p.Arg17Pro

c.50G>C · VCV4953662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9416 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,170,611)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9416	likely pathogenic · top 2% in EMD
REVEL	0.279	benign-leaning
SaProt	LLR -14.12	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	29.9	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

No allele count reported in gnomAD v4.1 (AN 1,170,611). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EMD
Protein: p.Arg17Pro
Coding: c.50G>C
MANE Select: NM_000117
Type: single nucleotide variant
Location: chrX:154379534 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 17: the lem domain; an α-helix

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

Similar variants

EMD p.Arg17His Uncertain significance ★ ⚠ same residue
EMD p.Arg17= Likely benign ★ same residue
EMD c.187+1G>A Pathogenic ★★ same type
EMD c.187+1G>T Pathogenic/Likely pathogenic ★★ same type
EMD c.265+1G>A Likely pathogenic ★★ same type
EMD c.265+2T>A Likely pathogenic ★★ same type
EMD c.266-2A>G Pathogenic ★★ same type
EMD c.266-3A>G Pathogenic ★★ same type

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-arg17pro (accessed [today's date]).

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