Is EMD p.Ser187Pro (c.559T>C) pathogenic?

EMD p.Ser187Pro (c.559T>C) is classified Uncertain significance in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2012-09-10). AlphaMissense: likely benign (0.1125); Very rare (popmax 0.000112%, nfe).

How common is EMD p.Ser187Pro (c.559T>C) in the general population?

EMD p.Ser187Pro (c.559T>C) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about EMD p.Ser187Pro (c.559T>C)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

EMD p.Ser187Pro

c.559T>C · rs794729012 · VCV201774

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -8.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.5	GERP -1.7, phastCons 0.22
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	17.88	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

Grpmax group 0.000112% European (non-Finnish) · 1/895,452 alleles

Overall 8.25e-05% 1/1,211,497 alleles · very rare exomes 1/1,097,984 · genomes 0/113,513 · 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.Ser187Pro
Coding: c.559T>C
MANE Select: NM_000117
dbSNP: rs794729012
Type: single nucleotide variant
Location: chrX:154380991 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 187: the 'interaction with f-actin' region

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

Similar variants

EMD p.Ser187= 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
EMD c.399+1G>T 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-ser187pro (accessed [today's date]).

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