Is ECEL1 p.Arg663Trp (c.1987C>T) pathogenic?

ECEL1 p.Arg663Trp (c.1987C>T) is classified Uncertain significance in ECEL1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-22). AlphaMissense: likely benign (0.1746); Very rare (popmax 0.00505%, amr); Associated with ECEL1-related disorder.

What condition is associated with ECEL1 p.Arg663Trp (c.1987C>T)?

ECEL1 p.Arg663Trp (c.1987C>T) is associated with ECEL1-related disorder (ClinVar).

How common is ECEL1 p.Arg663Trp (c.1987C>T) in the general population?

ECEL1 p.Arg663Trp (c.1987C>T) is very rare (popmax 0.00505%, amr) (gnomAD).

What do computational predictors say about ECEL1 p.Arg663Trp (c.1987C>T)?

AlphaMissense predicts likely benign (score 0.1746) — an in-silico prediction, not a clinical call.

ECEL1 p.Arg663Trp

c.1987C>T · rs768312431 · VCV3029901

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00505%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ECEL1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1746	likely benign
REVEL	0.687	pathogenic-leaning
SaProt	LLR -11.64	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.65	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.4	GERP 5.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	36.0	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 0.00505% Admixed American · 3/59,370 alleles

Filtering AF 0.00134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000672%

Overall 0.000746% 12/1,607,984 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00505%	19,790
European (non-Finnish)	0.000764%	130,837

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.Arg663Trp
Coding: c.1987C>T
MANE Select: NM_004826
dbSNP: rs768312431
Type: single nucleotide variant
Location: chr2:232481508 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 663: a disulfide bond; the peptidase m13 domain

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

Disease context

ECEL1-related disorder

Similar variants

ECEL1 p.Arg663Gln Uncertain significance ★ ⚠ same residue
ECEL1 p.Gln435Ter Pathogenic/Likely pathogenic ★★ same condition
ECEL1 p.Thr615Pro Likely pathogenic ★ same condition
ECEL1 p.Tyr618Ter Likely pathogenic ★ same condition
ECEL1 p.Val385= Likely pathogenic ★ same condition
ECEL1 p.Arg404Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
ECEL1 p.Leu733Pro Uncertain significance ★ ⚠ same condition
ECEL1 c.2228+4T>A Likely benign 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-arg663trp (accessed [today's date]).

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