Is ECE1 p.Thr385= (c.1155C>T) pathogenic?

ECE1 p.Thr385= (c.1155C>T) is classified Benign in ECE1 (ClinVar, Multiple submitters, 2 submitters). Common (popmax 26.9%, nfe) — too common for a highly-penetrant pathogenic allele.

ECE1 p.Thr385=

Q: How common is ECE1 p.Thr385= (c.1155C>T) in the general population?

ECE1 p.Thr385= (c.1155C>T) is common (popmax 26.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1155C>T · rs2229450 · VCV258080

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 26.9%, nfe) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -3.5
Overall
CADD	0.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.9% European (non-Finnish) · 317,417/1,179,914 alleles

Filtering AF 26.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.8%

Overall 24.5% 395,553/1,613,978 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	28%	4
European (non-Finnish)grpmax	26.9%	4
Finnishnot grpmax-eligible	26.1%	4
Middle Eastern	24.6%	4
Remaining individualsnot grpmax-eligible	22.6%	4
Admixed American	22.1%	5
Ashkenazi Jewishnot grpmax-eligible	21.3%	5
South Asian	17.4%	6
East Asian	14.3%	7
African / African-American	5%	20

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr385=
Coding: c.1155C>T
MANE Select: NM_001397
dbSNP: rs2229450
Type: single nucleotide variant
Location: chr1:21247229 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 91.16 · 1 PDB
Residue 385: 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.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
ECE1 p.Asp547= 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-thr385 (accessed [today's date]).

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