Is ELOA p.Arg253His (c.758G>A) pathogenic?

ELOA p.Arg253His (c.758G>A) is classified Uncertain significance in ELOA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). AlphaMissense: likely benign (0.0671); Rare (popmax 0.151%, nfe).

How common is ELOA p.Arg253His (c.758G>A) in the general population?

ELOA p.Arg253His (c.758G>A) is rare (popmax 0.151%, nfe) (gnomAD).

What do computational predictors say about ELOA p.Arg253His (c.758G>A)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

ELOA p.Arg253His

c.758G>A · VCV3508017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.151%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.024	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 5.7	GERP 0.67, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,276 bp · p 0.12 · regional, not allelic
Overall
CADD	15.2	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 R279H vs ClinVar R253H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.151% European (non-Finnish) · 1,783/1,180,024 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.143%

Overall 0.121% 1,949/1,614,194 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.151%	662
Remaining individualsnot grpmax-eligible	0.138%	727
Admixed American	0.06%	1,668
Finnishnot grpmax-eligible	0.0562%	1,778
African / African-American	0.00933%	10,723
South Asian	0.0011%	91,084

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.Arg253His
Coding: c.758G>A
MANE Select: NM_003198
Type: single nucleotide variant
Location: chr1:23751363 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 57.63 · 5 PDB
Residue 253: the 'disordered' region

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

Similar variants

ELOA p.Arg253Cys Uncertain significance ★ ⚠ same residue
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

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-arg253his (accessed [today's date]).

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