Is EMC1 p.Pro874fs (c.2619_2622del) pathogenic?

EMC1 p.Pro874fs (c.26192622del) is classified Pathogenic/Likely pathogenic in EMC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-16). Very rare (popmax 0.00334%, amr); Associated with congenital anomaly of kidney and urinary tract.

What condition is associated with EMC1 p.Pro874fs (c.2619_2622del)?

EMC1 p.Pro874fs (c.2619_2622del) is associated with congenital anomaly of kidney and urinary tract, cerebellar atrophy, visual impairment, and psychomotor retardation; (ClinVar).

How common is EMC1 p.Pro874fs (c.2619_2622del) in the general population?

EMC1 p.Pro874fs (c.2619_2622del) is very rare (popmax 0.00334%, amr) (gnomAD).

EMC1 p.Pro874fs

c.2619_2622del · rs869320624 · VCV219099

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

congenital anomaly of kidney and urinary tract

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 21 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,932 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00132% 2/151,596 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.Pro874fs
Coding: c.2619_2622del
MANE Select: NM_015047
dbSNP: rs869320624
Type: Deletion
Location: chr1:19220814 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 874: a β-strand

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

Disease context

congenital anomaly of kidney and urinary tract — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cerebellar atrophy, visual impairment, and psychomotor retardation;

Similar variants

EMC1 p.Asn739fs Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Pro874His Uncertain significance ★★ ⚠ same residue
EMC1 p.Val564fs Pathogenic ★ same condition
EMC1 c.2675_2676del Pathogenic/Likely pathogenic ★★ same condition
EMC1 c.287-1G>A Likely pathogenic ★★ same condition
EMC1 c.787-1G>A Likely pathogenic ★★ same condition
EMC1 p.Arg660Ter Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Arg69Ter 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-pro874fs (accessed [today's date]).

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