Is ECEL1 p.Cys760Arg (c.2278T>C) pathogenic?

ECEL1 p.Cys760Arg (c.2278T>C) is classified Pathogenic in ECEL1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-04-15). AlphaMissense: likely pathogenic (0.9961); Very rare (popmax 8.47e-05%, nfe); Associated with distal arthrogryposis type 5D.

What condition is associated with ECEL1 p.Cys760Arg (c.2278T>C)?

ECEL1 p.Cys760Arg (c.2278T>C) is associated with distal arthrogryposis type 5D (ClinVar).

How common is ECEL1 p.Cys760Arg (c.2278T>C) in the general population?

ECEL1 p.Cys760Arg (c.2278T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Distal arthrogryposis type 5D inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ECEL1 p.Cys760Arg (c.2278T>C)?

AlphaMissense predicts likely pathogenic (score 0.9961) — an in-silico prediction, not a clinical call.

ECEL1 p.Cys760Arg

c.2278T>C · rs587777129 · VCV100650

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

distal arthrogryposis type 5D

Computational evidence

Protein change
AlphaMissense	0.9961	likely pathogenic ✓ concordant with ClinVar · top 3% in ECEL1
REVEL	0.948	strongly pathogenic-leaning
SaProt	LLR -14.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 5.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	31.0	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 8.47e-05% European (non-Finnish) · 1/1,179,972 alleles

Overall 0.000658% 1/152,014 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: ECEL1
Protein: p.Cys760Arg
Coding: c.2278T>C
MANE Select: NM_004826
dbSNP: rs587777129
Type: single nucleotide variant
Location: chr2:232480203 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 760: a disulfide bond; a UniProt-annotated variant site (in da5d); the peptidase m13 domain

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

Disease context

distal arthrogryposis type 5D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Distal arthrogryposis type 5D (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

ECEL1 p.Cys760Phe Uncertain significance ★ ⚠ same residue
ECEL1 c.1685+1G>A Pathogenic ★★ same condition
ECEL1 c.2151+2T>C Likely pathogenic ★★ same condition
ECEL1 c.966+1G>A Pathogenic ★★ same condition
ECEL1 p.Ala675Thr Pathogenic ★★ same condition
ECEL1 p.Arg333Ter Pathogenic ★★ same condition
ECEL1 p.Arg395Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ECEL1 p.Arg418Cys Likely pathogenic ★★ 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-cys760arg (accessed [today's date]).

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