Is ECEL1 p.Arg404Cys (c.1210C>T) pathogenic?

ECEL1 p.Arg404Cys (c.1210C>T) is classified Conflicting classifications of pathogenicity in ECEL1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-09-01). AlphaMissense: likely pathogenic (0.8154); Very rare (popmax 0.00223%, eas); Associated with ECEL1-related disorders.

What condition is associated with ECEL1 p.Arg404Cys (c.1210C>T)?

ECEL1 p.Arg404Cys (c.1210C>T) is associated with ECEL1-related disorders, distal arthrogryposis type 5D (ClinVar).

How common is ECEL1 p.Arg404Cys (c.1210C>T) in the general population?

ECEL1 p.Arg404Cys (c.1210C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ECEL1 p.Arg404Cys (c.1210C>T)?

AlphaMissense predicts likely pathogenic (score 0.8154) — an in-silico prediction, not a clinical call.

ECEL1 p.Arg404Cys

c.1210C>T · rs532757890 · VCV191152

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8154 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ECEL1-related disorders

Computational evidence

Protein change
AlphaMissense	0.8154	likely pathogenic
REVEL	0.948	strongly pathogenic-leaning
SaProt	LLR -11.29	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 5.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	32.0	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 · 1/44,868 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000744% 12/1,612,578 alleles · very rare exomes 11/1,460,286 · genomes 1/152,292 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,868
South Asian	0.0022%	45,516
Admixed American	0.00167%	60,000
European (non-Finnish)	0.000678%	147,468

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.Arg404Cys
Coding: c.1210C>T
MANE Select: NM_004826
dbSNP: rs532757890
Type: single nucleotide variant
Location: chr2:232484198 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 404: 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

ECEL1-related disorders

Also linked: distal arthrogryposis type 5D

Similar variants

ECEL1 p.Arg404His Conflicting classifications of pathogenicity ★ 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-arg404cys (accessed [today's date]).

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