Is ELOA p.Pro727Arg (c.2180C>G) pathogenic?

ELOA p.Pro727Arg (c.2180C>G) is classified Uncertain significance in ELOA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: ambiguous (0.426); Very rare (popmax 8.48e-05%, nfe).

How common is ELOA p.Pro727Arg (c.2180C>G) in the general population?

ELOA p.Pro727Arg (c.2180C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ELOA p.Pro727Arg (c.2180C>G)?

AlphaMissense predicts ambiguous (score 0.426) — an in-silico prediction, not a clinical call.

ELOA p.Pro727Arg

c.2180C>G · rs1644797409 · VCV3088369

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.426 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.426	ambiguous
REVEL	0.221	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -0.39, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 3,273 bp · p 0.035 · regional, not allelic
Overall
CADD	25.1	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 P753R vs ClinVar P727R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,146 alleles

Overall 6.86e-05% 1/1,458,750 alleles · very rare

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.Pro727Arg
Coding: c.2180C>G
MANE Select: NM_003198
dbSNP: rs1644797409
Type: single nucleotide variant
Location: chr1:23757048 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 57.63 · 5 PDB
Residue 727: the 'disordered' 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-pro727arg (accessed [today's date]).

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