Is ELOA p.Arg642Gln (c.1925G>A) pathogenic?

ELOA p.Arg642Gln (c.1925G>A) is classified Uncertain significance in ELOA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.0763); Rare (popmax 0.13%, amr).

How common is ELOA p.Arg642Gln (c.1925G>A) in the general population?

ELOA p.Arg642Gln (c.1925G>A) is rare (popmax 0.13%, amr) (gnomAD).

What do computational predictors say about ELOA p.Arg642Gln (c.1925G>A)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

ELOA p.Arg642Gln

c.1925G>A · rs202158596 · VCV3088365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.13%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.071	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -1.6, phastCons 0.98
Regional constraint	o/e 0.34	constrained · MANE · 380 bp · p 4.2e-07 · regional, not allelic
Overall
CADD	17.67	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 R668Q vs ClinVar R642Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.13% Admixed American · 78/59,950 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0982%

Overall 0.0368% 594/1,613,846 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.13%	769
Remaining individualsnot grpmax-eligible	0.0496%	2,016
European (non-Finnish)	0.0405%	2,469
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
African / African-American	0.00534%	18,734

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: ELOA
Protein: p.Arg642Gln
Coding: c.1925G>A
MANE Select: NM_003198
dbSNP: rs202158596
Type: single nucleotide variant
Location: chr1:23755976 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 57.63 · 5 PDB
Residue 642: an α-helix; the 'activation domain' region

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

Similar variants

ELOA p.Pro620= Benign ★★ same type
ELOA c.-18G>C Uncertain significance ★ ⚠ same type
ELOA c.-29C>T Uncertain significance ★ ⚠ same type
ELOA c.-6A>G Uncertain significance ★ ⚠ same type
ELOA c.-8T>G Uncertain significance ★ ⚠ same type
ELOA p.Ala224Ser Uncertain significance ★ ⚠ same type
ELOA p.Ala430Pro Uncertain significance ★ ⚠ same type
ELOA p.Ala44Val 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/eloa-p-arg642gln (accessed [today's date]).

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