Is ECEL1 p.Phe111fs (c.332del) pathogenic?

ECEL1 p.Phe111fs (c.332del) is classified Likely pathogenic in ECEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-01). Very rare (popmax 0.00163%, nfe).

How common is ECEL1 p.Phe111fs (c.332del) in the general population?

ECEL1 p.Phe111fs (c.332del) is very rare (popmax 0.00163%, nfe) (gnomAD).

ECEL1 p.Phe111fs

c.332del · rs764471983 · VCV624185

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00163%, 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 2 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP -1.2, phastCons 1
Overall
CADD	27.4	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 0.00163% European (non-Finnish) · 19/1,169,020 alleles

Filtering AF 0.00104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000838%

Overall 0.0014% 22/1,575,910 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00393%	25,429
Remaining individualsnot grpmax-eligible	0.00163%	61,186
European (non-Finnish)grpmax	0.00163%	61,527

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ECEL1
Protein: p.Phe111fs
Coding: c.332del
MANE Select: NM_004826
dbSNP: rs764471983
Type: Deletion
Location: chr2:232486322 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 111: the peptidase m13 domain

Full ECEL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECEL1 p.Gly170fs Pathogenic ★★ same type
ECEL1 p.Gly27fs Pathogenic/Likely pathogenic ★★ same type
ECEL1 p.Phe37fs Pathogenic ★★ same type
ECEL1 p.Arg49_Ser50delinsPro Likely pathogenic ★ same type
ECEL1 p.Gln348fs Pathogenic ★ same type
ECEL1 p.Glu13fs Likely pathogenic ★ same type
ECEL1 p.Gly133fs Likely pathogenic ★ same type
ECEL1 p.Pro595_Asp596del 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/ecel1-p-phe111fs (accessed [today's date]).

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