Is ECEL1 p.Val385= (c.1155G>A) pathogenic?

ECEL1 p.Val385= (c.1155G>A) is classified Likely pathogenic in ECEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-14). Very rare (popmax 0.000657%); Associated with ECEL1-related disorders.

What condition is associated with ECEL1 p.Val385= (c.1155G>A)?

ECEL1 p.Val385= (c.1155G>A) is associated with ECEL1-related disorders (ClinVar).

How common is ECEL1 p.Val385= (c.1155G>A) in the general population?

ECEL1 p.Val385= (c.1155G>A) is very rare (popmax 0.000657%) (gnomAD).

ECEL1 p.Val385=

c.1155G>A · VCV4960552

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000657%)

Conditions

ECEL1-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.63	donor gain · deltas
Pangolin	Δ0.76	gain · loss 0.70 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.7	GERP 0.6, phastCons 1
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000657%

Overall 0.000657% 1/152,228 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.Val385=
Coding: c.1155G>A
MANE Select: NM_004826
Type: single nucleotide variant
Location: chr2:232484501 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 385: a disulfide bond; the peptidase m13 domain

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

Disease context

ECEL1-related disorders

Similar variants

ECEL1 p.Val385Met Uncertain significance ★ same residue
ECEL1 p.Gln435Ter Pathogenic/Likely pathogenic ★★ same condition
ECEL1 p.Thr615Pro Likely pathogenic ★ same condition
ECEL1 p.Tyr618Ter Likely pathogenic ★ same condition
ECEL1 p.Arg404Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
ECEL1 p.Leu733Pro Uncertain significance ★ ⚠ same condition
ECEL1 p.Arg663Trp Uncertain significance ⚠ same condition
ECEL1 c.2228+4T>A Likely benign 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-val385 (accessed [today's date]).

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