Is ELOA p.Arg253Cys (c.757C>T) pathogenic?

ELOA p.Arg253Cys (c.757C>T) is classified Uncertain significance in ELOA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely benign (0.0784); Ultra-rare (popmax 0.0267%, eas).

How common is ELOA p.Arg253Cys (c.757C>T) in the general population?

ELOA p.Arg253Cys (c.757C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about ELOA p.Arg253Cys (c.757C>T)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

ELOA p.Arg253Cys

c.757C>T · VCV4017606

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.033	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 4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,276 bp · p 0.12 · regional, not allelic
Overall
CADD	19.44	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 R279C vs ClinVar R253C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,884 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00186% 30/1,614,200 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,740
South Asian	0.0022%	45,545
African / African-American	0.00133%	75,068
European (non-Finnish)	0.00127%	78,669

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.Arg253Cys
Coding: c.757C>T
MANE Select: NM_003198
Type: single nucleotide variant
Location: chr1:23751362 (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.Arg253His 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-arg253cys (accessed [today's date]).

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