Is ECHDC3 p.Phe172Val (c.514T>G) pathogenic?

ECHDC3 p.Phe172Val (c.514T>G) is classified Uncertain significance in ECHDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). AlphaMissense: likely pathogenic (0.7808); Very rare (popmax 0.000932%, nfe).

How common is ECHDC3 p.Phe172Val (c.514T>G) in the general population?

ECHDC3 p.Phe172Val (c.514T>G) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about ECHDC3 p.Phe172Val (c.514T>G)?

AlphaMissense predicts likely pathogenic (score 0.7808) — an in-silico prediction, not a clinical call.

ECHDC3 p.Phe172Val

c.514T>G · rs1175644220 · VCV2280798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7808 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7808	likely pathogenic
REVEL	0.84	moderately pathogenic-leaning
SaProt	LLR -14.61	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 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 21 kb · p 0.0091 · regional, not allelic
Overall
CADD	26.5	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

Grpmax group 0.000932% European (non-Finnish) · 11/1,180,010 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000889% 13/1,461,860 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)grpmax	0.000932%	107,274

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe172Val
Coding: c.514T>G
MANE Select: NM_024693
dbSNP: rs1175644220
Type: single nucleotide variant
Location: chr10:11755531 (GRCh38)
Gene constraint: LOEUF 1.614 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.44 · 1 PDB
Residue 172: 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-phe172val (accessed [today's date]).

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