Is ECEL1 p.Pro513Leu (c.1538C>T) pathogenic?

ECEL1 p.Pro513Leu (c.1538C>T) is classified Uncertain significance in ECEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: likely pathogenic (0.9839); Very rare (popmax 0.00224%, eas); Associated with distal arthrogryposis.

What condition is associated with ECEL1 p.Pro513Leu (c.1538C>T)?

ECEL1 p.Pro513Leu (c.1538C>T) is associated with distal arthrogryposis (ClinVar).

How common is ECEL1 p.Pro513Leu (c.1538C>T) in the general population?

ECEL1 p.Pro513Leu (c.1538C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about ECEL1 p.Pro513Leu (c.1538C>T)?

AlphaMissense predicts likely pathogenic (score 0.9839) — an in-silico prediction, not a clinical call.

ECEL1 p.Pro513Leu

c.1538C>T · VCV3899303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9839 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

distal arthrogryposis

Computational evidence

Protein change
AlphaMissense	0.9839	likely pathogenic · top 9% in ECEL1
REVEL	0.87	moderately pathogenic-leaning
SaProt	LLR -15.99	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 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

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,634 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.00106% 17/1,608,488 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,634
South Asian	0.00222%	45,132
Admixed American	0.0017%	58,678
Remaining individualsnot grpmax-eligible	0.00161%	62,288
European (non-Finnish)	0.00102%	98,169

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.Pro513Leu
Coding: c.1538C>T
MANE Select: NM_004826
Type: single nucleotide variant
Location: chr2:232483148 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 513: 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.Pro513= Likely benign ★ same residue
ECEL1 p.Arg484Cys 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-pro513leu (accessed [today's date]).

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