Is ECHDC1 p.Arg192Gln (c.575G>A) pathogenic?

ECHDC1 p.Arg192Gln (c.575G>A) is classified Uncertain significance in ECHDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: ambiguous (0.3762); Ultra-rare (popmax 0.0329%, mid).

How common is ECHDC1 p.Arg192Gln (c.575G>A) in the general population?

ECHDC1 p.Arg192Gln (c.575G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about ECHDC1 p.Arg192Gln (c.575G>A)?

AlphaMissense predicts ambiguous (score 0.3762) — an in-silico prediction, not a clinical call.

ECHDC1 p.Arg192Gln

c.575G>A · rs763356475 · VCV2389861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3762 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3762	ambiguous
REVEL	0.757	pathogenic-leaning
SaProt	LLR -11.99	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 41 kb · p 0.24 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R198Q vs ClinVar R192Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,078 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00248% 40/1,613,526 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,039
East Asian	0.029%	3,451
Remaining individualsnot grpmax-eligible	0.0064%	15,619
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,584
Admixed American	0.00167%	59,894
European (non-Finnish)	0.00153%	65,542
South Asian	0.0011%	91,064

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: ECHDC1
Protein: p.Arg192Gln
Coding: c.575G>A
MANE Select: NM_001002030
dbSNP: rs763356475
Type: single nucleotide variant
Location: chr6:127290200 (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.Arg99His Uncertain significance ★ ⚠ same type
ECHDC1 p.Cys262Phe Uncertain significance ★ ⚠ same type
ECHDC1 p.Gln228His Uncertain significance ★ ⚠ same type
ECHDC1 p.Gln274His 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-arg192gln (accessed [today's date]).

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