Is ECHDC2 p.Glu276Gln (c.826G>C) pathogenic?

ECHDC2 p.Glu276Gln (c.826G>C) is classified Uncertain significance in ECHDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely pathogenic (0.7223); Absent from gnomAD v4.1.

How common is ECHDC2 p.Glu276Gln (c.826G>C) in the general population?

ECHDC2 p.Glu276Gln (c.826G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ECHDC2 p.Glu276Gln (c.826G>C)?

AlphaMissense predicts likely pathogenic (score 0.7223) — an in-silico prediction, not a clinical call.

ECHDC2 p.Glu276Gln

c.826G>C · rs758715179 · VCV3086944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7223 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7223	likely pathogenic
REVEL	0.825	moderately pathogenic-leaning
SaProt	LLR -13.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 25 kb · p 0.66 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ECHDC2
Protein: p.Glu276Gln
Coding: c.826G>C
MANE Select: NM_001198961
dbSNP: rs758715179
Type: single nucleotide variant
Location: chr1:52896573 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.28

Full ECHDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECHDC2 p.Ala105Val Uncertain significance ★ ⚠ same type
ECHDC2 p.Ala131Val Uncertain significance ★ ⚠ same type
ECHDC2 p.Ala152Thr Uncertain significance ★ ⚠ same type
ECHDC2 p.Ala201Gly Uncertain significance ★ ⚠ same type
ECHDC2 p.Ala20Pro Uncertain significance ★ ⚠ same type
ECHDC2 p.Ala20Thr Uncertain significance ★ ⚠ same type
ECHDC2 p.Ala210Thr Uncertain significance ★ ⚠ same type
ECHDC2 p.Ala219Thr 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/echdc2-p-glu276gln (accessed [today's date]).

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