Is ECHDC2 p.Asn119Ser (c.356A>G) pathogenic?

ECHDC2 p.Asn119Ser (c.356A>G) is classified Uncertain significance in ECHDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: likely benign (0.1016); Very rare (popmax 0.00168%, amr).

How common is ECHDC2 p.Asn119Ser (c.356A>G) in the general population?

ECHDC2 p.Asn119Ser (c.356A>G) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about ECHDC2 p.Asn119Ser (c.356A>G)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

ECHDC2 p.Asn119Ser

c.356A>G · VCV4016025

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -4.62	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 0.72	GERP -2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 25 kb · p 0.66 · regional, not allelic
Overall
CADD	9.892	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 0.00168% Admixed American · 1/59,500 alleles

Overall 0.000127% 2/1,578,492 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,500
African / African-American	0.00135%	73,834

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: ECHDC2
Protein: p.Asn119Ser
Coding: c.356A>G
MANE Select: NM_001198961
Type: single nucleotide variant
Location: chr1:52907876 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.28
Residue 119: a UniProt-annotated variant site (in)

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-asn119ser (accessed [today's date]).

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