Is ECEL1 p.Arg395Gln (c.1184G>A) pathogenic?

ECEL1 p.Arg395Gln (c.1184G>A) is classified Pathogenic/Likely pathogenic in ECEL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-18). AlphaMissense: likely benign (0.1153); Very rare (popmax 0.00223%, eas); Associated with distal arthrogryposis type 5D.

What condition is associated with ECEL1 p.Arg395Gln (c.1184G>A)?

ECEL1 p.Arg395Gln (c.1184G>A) is associated with distal arthrogryposis type 5D (ClinVar).

How common is ECEL1 p.Arg395Gln (c.1184G>A) in the general population?

ECEL1 p.Arg395Gln (c.1184G>A) is very rare (popmax 0.00223%, eas) (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.Arg395Gln (c.1184G>A)?

AlphaMissense predicts likely benign (score 0.1153) — an in-silico prediction, not a clinical call.

ECEL1 p.Arg395Gln

c.1184G>A · rs765430577 · VCV235819

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1153 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

distal arthrogryposis type 5D

Computational evidence

Protein change
AlphaMissense	0.1153	likely benign ⚠ discordant with ClinVar
REVEL	0.409	indeterminate
SaProt	LLR -7.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.64	donor gain · deltas
Pangolin	Δ0.69	loss · gain 0.58 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 5.7	GERP -2.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	35.0	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 0.00223% East Asian · 1/44,866 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000411% 6/1,461,240 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,866
South Asian	0.0011%	91,072
European (non-Finnish)	0.000339%	294,941

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.Arg395Gln
Coding: c.1184G>A
MANE Select: NM_004826
dbSNP: rs765430577
Type: single nucleotide variant
Location: chr2:232484472 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 395: 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.Arg418Cys Likely pathogenic ★★ same condition
ECEL1 p.Gln435Ter Pathogenic/Likely pathogenic ★★ same condition
ECEL1 p.Gly511Ser 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-arg395gln (accessed [today's date]).

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