Is EMC1 p.Ser270fs (c.808dup) pathogenic?

EMC1 p.Ser270fs (c.808dup) is classified Pathogenic in EMC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). Very rare (popmax 0.00102%, nfe).

How common is EMC1 p.Ser270fs (c.808dup) in the general population?

EMC1 p.Ser270fs (c.808dup) is very rare (popmax 0.00102%, nfe) (gnomAD).

EMC1 p.Ser270fs

c.808dup · rs1220641407 · VCV1455289

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

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 8 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 0.76, phastCons 1
Overall
CADD	28.0	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 0.00102% European (non-Finnish) · 12/1,179,056 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000744% 12/1,612,422 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.Ser270fs
Coding: c.808dup
MANE Select: NM_015047
dbSNP: rs1220641407
Type: Duplication
Location: chr1:19239963 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB

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

Similar variants

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.Arg141fs Pathogenic ★ 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-ser270fs (accessed [today's date]).

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