Is ECEL1 p.Met382Ile (c.1146G>A) pathogenic?

ECEL1 p.Met382Ile (c.1146G>A) is classified Conflicting classifications of pathogenicity in ECEL1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-23). AlphaMissense: likely pathogenic (0.5923); Ultra-rare (popmax 0.0185%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ECEL1 p.Met382Ile (c.1146G>A)?

ECEL1 p.Met382Ile (c.1146G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ECEL1 p.Met382Ile (c.1146G>A) in the general population?

ECEL1 p.Met382Ile (c.1146G>A) is ultra-rare (popmax 0.0185%, nfe) (gnomAD).

What do computational predictors say about ECEL1 p.Met382Ile (c.1146G>A)?

AlphaMissense predicts likely pathogenic (score 0.5923) — an in-silico prediction, not a clinical call.

ECEL1 p.Met382Ile

c.1146G>A · rs140675806 · VCV2153982

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5923 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0185%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5923	likely pathogenic
REVEL	0.193	benign-leaning
SaProt	LLR -3.29	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.57, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0185% European (non-Finnish) · 218/1,180,024 alleles

Filtering AF 0.0165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.0141% 228/1,613,834 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0185%	5,413
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Finnishnot grpmax-eligible	0.00314%	31,895
African / African-American	0.00267%	37,465
Admixed American	0.00167%	60,014

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.Met382Ile
Coding: c.1146G>A
MANE Select: NM_004826
dbSNP: rs140675806
Type: single nucleotide variant
Location: chr2:232484510 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 382: a disulfide bond; the peptidase m13 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ECEL1 p.Arg756Trp Uncertain significance ★★ ⚠ same condition
ECEL1 p.Gly209Val Uncertain significance ★★ ⚠ same condition
ECEL1 p.Pro34Ser Uncertain significance ★★ ⚠ same condition
ECEL1 p.Ser44Arg Uncertain significance ★★ ⚠ same condition
ECEL1 p.Arg355Gln Likely benign ★★ same condition
ECEL1 c.1990-6C>T Conflicting classifications of pathogenicity ★ same condition
ECEL1 p.Ala109Val Uncertain significance ★ ⚠ same condition
ECEL1 p.Ala175Thr Uncertain significance ★ ⚠ 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/ecel1-p-met382ile (accessed [today's date]).

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