Is EMC1 p.Ser747fs (c.2239_2240del) pathogenic?

EMC1 p.Ser747fs (c.22392240del) is classified Pathogenic/Likely pathogenic in EMC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-11). Very rare (popmax 0.000169%, nfe); Associated with EMC1-related disorder.

What condition is associated with EMC1 p.Ser747fs (c.2239_2240del)?

EMC1 p.Ser747fs (c.2239_2240del) is associated with EMC1-related disorder (ClinVar).

How common is EMC1 p.Ser747fs (c.2239_2240del) in the general population?

EMC1 p.Ser747fs (c.2239_2240del) is very rare (popmax 0.000169%, nfe) (gnomAD).

EMC1 p.Ser747fs

c.2239_2240del · rs773033814 · VCV1452472

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

EMC1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 19 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 1.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,040 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,820 alleles · very rare

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: EMC1
Protein: p.Ser747fs
Coding: c.2239_2240del
MANE Select: NM_015047
dbSNP: rs773033814
Type: Microsatellite
Location: chr1:19223532 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 747: a β-strand

Full EMC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EMC1-related disorder

Similar variants

EMC1 c.2675_2676del Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Glu746fs Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Tyr179fs Likely pathogenic ★ same condition
EMC1 p.Ser747Arg Uncertain significance ★ ⚠ same residue
EMC1 p.Ser747Asn Uncertain significance ★ ⚠ same residue
EMC1 p.Ala188fs Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Arg105Ter Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Arg660Ter Pathogenic/Likely pathogenic ★★ 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/emc1-p-ser747fs (accessed [today's date]).

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