Is ECEL1 p.Arg484Cys (c.1450C>T) pathogenic?

ECEL1 p.Arg484Cys (c.1450C>T) is classified Uncertain significance in ECEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: likely benign (0.2828); Very rare (popmax 0.00475%, nfe); Associated with distal arthrogryposis.

What condition is associated with ECEL1 p.Arg484Cys (c.1450C>T)?

ECEL1 p.Arg484Cys (c.1450C>T) is associated with distal arthrogryposis (ClinVar).

How common is ECEL1 p.Arg484Cys (c.1450C>T) in the general population?

ECEL1 p.Arg484Cys (c.1450C>T) is very rare (popmax 0.00475%, nfe) (gnomAD).

What do computational predictors say about ECEL1 p.Arg484Cys (c.1450C>T)?

AlphaMissense predicts likely benign (score 0.2828) — an in-silico prediction, not a clinical call.

ECEL1 p.Arg484Cys

c.1450C>T · VCV3899304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2828 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00475%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

distal arthrogryposis

Computational evidence

Protein change
AlphaMissense	0.2828	likely benign
REVEL	0.649	pathogenic-leaning
SaProt	LLR -12.15	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	33.0	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 0.00475% European (non-Finnish) · 56/1,179,698 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00465% 75/1,612,216 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.016%	6,245
Finnishnot grpmax-eligible	0.00476%	21,004
European (non-Finnish)grpmax	0.00475%	21,066
South Asian	0.0044%	22,726
East Asian	0.00223%	44,820
African / African-American	0.00133%	74,998

Remaining individuals 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.Arg484Cys
Coding: c.1450C>T
MANE Select: NM_004826
Type: single nucleotide variant
Location: chr2:232483472 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 484: a disulfide bond; the peptidase m13 domain

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

Disease context

distal arthrogryposis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ECEL1 p.Arg484His Uncertain significance ★ ⚠ same residue
ECEL1 p.Pro513Leu Uncertain significance ★ ⚠ same condition
ECEL1 c.1685+1G>A Pathogenic ★★ same type
ECEL1 c.2151+2T>C Likely pathogenic ★★ same type
ECEL1 c.966+1G>A Pathogenic ★★ same type
ECEL1 p.Ala675Thr Pathogenic ★★ same type
ECEL1 p.Arg333Ter Pathogenic ★★ same type
ECEL1 p.Arg395Gln Pathogenic/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-arg484cys (accessed [today's date]).

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