Is EMC1 p.Arg141fs (c.412_419dup) pathogenic?

EMC1 p.Arg141fs (c.412419dup) is classified Pathogenic in EMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-23). Very rare (popmax 0.00133%, afr).

How common is EMC1 p.Arg141fs (c.412_419dup) in the general population?

EMC1 p.Arg141fs (c.412_419dup) is very rare (popmax 0.00133%, afr) (gnomAD).

EMC1 p.Arg141fs

c.412_419dup · rs1193333328 · VCV1460429

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 5 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,022 alleles

Overall 6.84e-05% 1/1,461,882 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.Arg141fs
Coding: c.412_419dup
MANE Select: NM_015047
dbSNP: rs1193333328
Type: Duplication
Location: chr1:19242434 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 141: a β-strand

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

Similar variants

EMC1 p.Ser270fs Pathogenic ★★ same type
EMC1 p.Tyr181Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg990fs Uncertain significance ★★ same type
EMC1 c.96-6dup Benign/Likely benign ★★ same type
EMC1 p.Ile769fs Likely pathogenic ★ same type
EMC1 p.Ile856fs Pathogenic ★ same type
EMC1 p.Ile896fs Pathogenic ★ same type
EMC1 p.Lys986Ter Likely 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/emc1-p-arg141fs (accessed [today's date]).

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