Is ECHDC3 p.Ser97Ala (c.289T>G) pathogenic?

ECHDC3 p.Ser97Ala (c.289T>G) is classified Uncertain significance in ECHDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-13). AlphaMissense: likely benign (0.0817); Ultra-rare (popmax 0.0379%, eas).

How common is ECHDC3 p.Ser97Ala (c.289T>G) in the general population?

ECHDC3 p.Ser97Ala (c.289T>G) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

What do computational predictors say about ECHDC3 p.Ser97Ala (c.289T>G)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

ECHDC3 p.Ser97Ala

c.289T>G · rs780276308 · VCV2473717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -10.48	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 5.2	GERP 1.1, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 21 kb · p 0.0091 · regional, not allelic
Overall
CADD	17.02	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 0.0379% East Asian · 17/44,880 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00105% 17/1,613,524 alleles · ultra-rare

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: ECHDC3
Protein: p.Ser97Ala
Coding: c.289T>G
MANE Select: NM_024693
dbSNP: rs780276308
Type: single nucleotide variant
Location: chr10:11747467 (GRCh38)
Gene constraint: LOEUF 1.614 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.44 · 1 PDB
Residue 97: a β-strand

Full ECHDC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECHDC3 p.Ala173Thr Uncertain significance ★ ⚠ same type
ECHDC3 p.Ala36Gly Uncertain significance ★ ⚠ same type
ECHDC3 p.Arg118His Uncertain significance ★ ⚠ same type
ECHDC3 p.Arg29Cys Uncertain significance ★ ⚠ same type
ECHDC3 p.Arg29His Uncertain significance ★ ⚠ same type
ECHDC3 p.Arg51Gly Uncertain significance ★ ⚠ same type
ECHDC3 p.Arg51Trp Uncertain significance ★ ⚠ same type
ECHDC3 p.Arg8Gln 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/echdc3-p-ser97ala (accessed [today's date]).

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