Is ECH1 c.349+9C>G pathogenic?

ECH1 c.349+9C>G is classified Uncertain significance in ECH1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-01-04). Rare (popmax 0.333%, nfe).

How common is ECH1 c.349+9C>G in the general population?

ECH1 c.349+9C>G is rare (popmax 0.333%, nfe) (gnomAD).

ECH1 c.349+9C>G

rs201526955 · VCV559114

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.333%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.097	GERP -4
Non-coding constraint	Z 1.05	1 kb window · o/e 0.93 · regional · uncalibrated
Overall
CADD	2.779	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.333% European (non-Finnish) · 3,932/1,179,260 alleles

Filtering AF 0.325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.321%

Overall 0.289% 4,658/1,613,182 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.348%	287
European (non-Finnish)grpmax	0.333%	300
Remaining individualsnot grpmax-eligible	0.33%	303
Amishnot grpmax-eligible	0.33%	303
Finnishnot grpmax-eligible	0.213%	470
South Asian	0.21%	477
Admixed American	0.075%	1,333
African / African-American	0.0534%	1,874
Middle Eastern	0.0165%	6,056
East Asian	0.00223%	44,870

Ashkenazi Jewish 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: ECH1
Coding: c.349+9C>G
MANE Select: NM_001398
dbSNP: rs201526955
Type: single nucleotide variant
Location: chr19:38831069 (GRCh38)
Gene constraint: LOEUF 1.083 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 2 PDB

Full ECH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECH1 p.Lys95Arg Uncertain significance ★★ ⚠ same type
ECH1 p.Ala226Thr Uncertain significance ★ ⚠ same type
ECH1 p.Ala237Val Uncertain significance ★ ⚠ same type
ECH1 p.Ala259Thr Uncertain significance ★ ⚠ same type
ECH1 p.Ala3Thr Uncertain significance ★ ⚠ same type
ECH1 p.Ala50Thr Uncertain significance ★ ⚠ same type
ECH1 p.Arg137Trp Uncertain significance ★ ⚠ same type
ECH1 p.Arg143His Uncertain significance ★ ⚠ 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/ech1-c-349-plus-9c-g (accessed [today's date]).

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