Is ECHDC1 p.Ser4Arg (c.12T>A) pathogenic?

ECHDC1 p.Ser4Arg (c.12T>A) is classified Uncertain significance in ECHDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.1689); Absent from gnomAD v4.1.

How common is ECHDC1 p.Ser4Arg (c.12T>A) in the general population?

ECHDC1 p.Ser4Arg (c.12T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ECHDC1 p.Ser4Arg (c.12T>A)?

AlphaMissense predicts likely benign (score 0.1689) — an in-silico prediction, not a clinical call.

ECHDC1 p.Ser4Arg

c.12T>A · rs2482072693 · VCV2238849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1689 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,936)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1689	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -5.96	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 3.3	GERP 0.66, phastCons 0.99
Regional constraint	o/e 0.94	unconstrained · MANE · 41 kb · p 0.24 · regional, not allelic
Overall
CADD	15.01	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S10R vs ClinVar S4R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,936). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ECHDC1
Protein: p.Ser4Arg
Coding: c.12T>A
MANE Select: NM_001002030
dbSNP: rs2482072693
Type: single nucleotide variant
Location: chr6:127331017 (GRCh38)
Gene constraint: LOEUF 1.452 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.84

Full ECHDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECHDC1 p.Met130Thr Likely pathogenic ★ same type
ECHDC1 c.-3+979G>C Uncertain significance ★ ⚠ same type
ECHDC1 p.Ala101Val Uncertain significance ★ ⚠ same type
ECHDC1 p.Ala272Thr Uncertain significance ★ ⚠ same type
ECHDC1 p.Arg192Gln Uncertain significance ★ ⚠ same type
ECHDC1 p.Arg99His Uncertain significance ★ ⚠ same type
ECHDC1 p.Cys262Phe Uncertain significance ★ ⚠ same type
ECHDC1 p.Gln228His 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/echdc1-p-ser4arg (accessed [today's date]).

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