Is ECEL1 p.Gln384Pro (c.1151A>C) pathogenic?

ECEL1 p.Gln384Pro (c.1151A>C) is classified Likely pathogenic in ECEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-15). AlphaMissense: likely pathogenic (0.5822); Absent from gnomAD v4.1; Associated with distal arthrogryposis type 5D.

What condition is associated with ECEL1 p.Gln384Pro (c.1151A>C)?

ECEL1 p.Gln384Pro (c.1151A>C) is associated with distal arthrogryposis type 5D (ClinVar).

How common is ECEL1 p.Gln384Pro (c.1151A>C) in the general population?

ECEL1 p.Gln384Pro (c.1151A>C) is absent from gnomAD v4.1 (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.Gln384Pro (c.1151A>C)?

AlphaMissense predicts likely pathogenic (score 0.5822) — an in-silico prediction, not a clinical call.

ECEL1 p.Gln384Pro

c.1151A>C · rs1690668690 · VCV2506357

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5822 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

distal arthrogryposis type 5D

Computational evidence

Protein change
AlphaMissense	0.5822	likely pathogenic ✓ concordant with ClinVar
REVEL	0.513	indeterminate
SaProt	LLR -14.03	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.37	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	23.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ECEL1
Protein: p.Gln384Pro
Coding: c.1151A>C
MANE Select: NM_004826
dbSNP: rs1690668690
Type: single nucleotide variant
Location: chr2:232484505 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 384: 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 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 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
ECEL1 p.Gln435Ter Pathogenic/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-gln384pro (accessed [today's date]).

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