Is ECE1 p.Asp522= (c.1566C>T) pathogenic?

ECE1 p.Asp522= (c.1566C>T) is classified Likely benign in ECE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Rare (popmax 0.325%, afr).

How common is ECE1 p.Asp522= (c.1566C>T) in the general population?

ECE1 p.Asp522= (c.1566C>T) is rare (popmax 0.325%, afr) (gnomAD).

ECE1 p.Asp522=

c.1566C>T · rs28368018 · VCV728171

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.325%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9	GERP -3.8
Overall
CADD	0.028	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.325% African / African-American · 244/75,038 alleles

Filtering AF 0.292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.279%

Overall 0.022% 355/1,614,132 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.325%	308
Admixed American	0.0417%	2,401
Remaining individualsnot grpmax-eligible	0.0336%	2,977
Middle Eastern	0.0165%	6,060
South Asian	0.00878%	11,386
European (non-Finnish)	0.00475%	21,071

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: ECE1
Protein: p.Asp522=
Coding: c.1566C>T
MANE Select: NM_001397
dbSNP: rs28368018
Type: single nucleotide variant
Location: chr1:21235850 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 91.16 · 1 PDB
Residue 522: a disulfide bond; the peptidase m13 domain

Full ECE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECE1 p.Asp522Gly Uncertain significance ★ ⚠ same residue
ECE1 p.Thr312Met Uncertain significance ★★ ⚠ same type
ECE1 c.1020+15G>A Benign ★★ same type
ECE1 c.1164-5C>T Benign ★★ same type
ECE1 c.1278+7C>T Benign ★★ same type
ECE1 c.1782-4C>A Benign ★★ same type
ECE1 c.828+8T>C Benign ★★ same type
ECE1 p.Asn397Ser Benign ★★ 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/ece1-p-asp522 (accessed [today's date]).

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