Is ECHDC3 p.Ser105Phe (c.314C>T) pathogenic?

ECHDC3 p.Ser105Phe (c.314C>T) is classified Uncertain significance in ECHDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). AlphaMissense: likely pathogenic (0.6094); Absent from gnomAD v4.1.

How common is ECHDC3 p.Ser105Phe (c.314C>T) in the general population?

ECHDC3 p.Ser105Phe (c.314C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ECHDC3 p.Ser105Phe (c.314C>T)?

AlphaMissense predicts likely pathogenic (score 0.6094) — an in-silico prediction, not a clinical call.

ECHDC3 p.Ser105Phe

c.314C>T · rs2492233002 · VCV2489626

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6094 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6094	likely pathogenic
REVEL	0.63	indeterminate
SaProt	LLR -13.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 21 kb · p 0.0091 · regional, not allelic
Overall
CADD	33.0	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: ECHDC3
Protein: p.Ser105Phe
Coding: c.314C>T
MANE Select: NM_024693
dbSNP: rs2492233002
Type: single nucleotide variant
Location: chr10:11749516 (GRCh38)
Gene constraint: LOEUF 1.614 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.44 · 1 PDB

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-ser105phe (accessed [today's date]).

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