Is ECH1 p.Asp284Asn (c.850G>A) pathogenic?

ECH1 p.Asp284Asn (c.850G>A) is classified Benign in ECH1 (ClinVar, Single submitter, 2 submitters). AlphaMissense: likely benign (0.1134); Common (popmax 9.39%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ECH1 p.Asp284Asn (c.850G>A)?

AlphaMissense predicts likely benign (score 0.1134) — an in-silico prediction, not a clinical call.

ECH1 p.Asp284Asn

Q: How common is ECH1 p.Asp284Asn (c.850G>A) in the general population?

ECH1 p.Asp284Asn (c.850G>A) is common (popmax 9.39%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.850G>A · rs58750431 · VCV559110

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1134 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.39%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1134	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -10.06	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -2.7
Regional constraint	o/e 1.03	unconstrained · MANE · 16 kb · p 0.49 · regional, not allelic
Overall
CADD	13.74	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 9.39% East Asian · 4,214/44,874 alleles

Filtering AF 9.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.06%

Overall 0.883% 14,245/1,614,150 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	9.39%	11
South Asian	7.96%	13
Remaining individualsnot grpmax-eligible	1.27%	79
Admixed American	1.16%	86
Finnishnot grpmax-eligible	1.1%	91
Middle Eastern	0.627%	160
Ashkenazi Jewishnot grpmax-eligible	0.402%	249
African / African-American	0.0653%	1,532
European (non-Finnish)	0.0325%	3,081

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
Protein: p.Asp284Asn
Coding: c.850G>A
MANE Select: NM_001398
dbSNP: rs58750431
Type: single nucleotide variant
Location: chr19:38815889 (GRCh38)
Gene constraint: LOEUF 1.083 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 2 PDB
Residue 284: an α-helix

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-p-asp284asn (accessed [today's date]).

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