Is ECHS1 p.Asp63Asn (c.187G>A) pathogenic?

ECHS1 p.Asp63Asn (c.187G>A) is classified Uncertain significance in ECHS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-06). AlphaMissense: likely benign (0.0913); Ultra-rare (popmax 0.0178%, eas).

How common is ECHS1 p.Asp63Asn (c.187G>A) in the general population?

ECHS1 p.Asp63Asn (c.187G>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about ECHS1 p.Asp63Asn (c.187G>A)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

ECHS1 p.Asp63Asn

c.187G>A · rs763796581 · VCV1441402

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -3.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1
Regional constraint	o/e 0.96	unconstrained · MANE · 10 kb · p 0.4 · regional, not allelic
Overall
CADD	1.598	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,880 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00155% 25/1,613,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,610
South Asian	0.00659%	15,173
African / African-American	0.004%	24,987
Remaining individualsnot grpmax-eligible	0.0016%	62,466
European (non-Finnish)	0.000593%	168,550

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: ECHS1
Protein: p.Asp63Asn
Coding: c.187G>A
MANE Select: NM_004092
dbSNP: rs763796581
Type: single nucleotide variant
Location: chr10:133370659 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.54 · 6 PDB
Residue 63: an α-helix

Full ECHS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECHS1 p.Asp63His Uncertain significance ★ ⚠ same residue
ECHS1 c.414+1G>A Pathogenic/Likely pathogenic ★★ same type
ECHS1 c.88+5G>A Pathogenic/Likely pathogenic ★★ same type
ECHS1 p.Ala132Thr Pathogenic/Likely pathogenic ★★ same type
ECHS1 p.Ala173Val Pathogenic/Likely pathogenic ★★ ⚠ same type
ECHS1 p.Ala238Val Pathogenic/Likely pathogenic ★★ ⚠ same type
ECHS1 p.Ala278Thr Likely pathogenic ★★ same type
ECHS1 p.Ala2Val Pathogenic ★★ ⚠ 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/echs1-p-asp63asn (accessed [today's date]).

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