Is ELOA p.Val751Leu (c.2251G>C) pathogenic?

ELOA p.Val751Leu (c.2251G>C) is classified Uncertain significance in ELOA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely pathogenic (0.6939); Ultra-rare (popmax 0.0862%, afr).

How common is ELOA p.Val751Leu (c.2251G>C) in the general population?

ELOA p.Val751Leu (c.2251G>C) is ultra-rare (popmax 0.0862%, afr) (gnomAD).

What do computational predictors say about ELOA p.Val751Leu (c.2251G>C)?

AlphaMissense predicts likely pathogenic (score 0.6939) — an in-silico prediction, not a clinical call.

ELOA p.Val751Leu

c.2251G>C · rs145432831 · VCV3088371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6939 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0862%, afr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.6939	likely pathogenic
REVEL	0.154	moderately benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.68, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 3,273 bp · p 0.035 · regional, not allelic
Overall
CADD	26.1	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 V777L vs ClinVar V751L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0862% African / African-American · 62/71,894 alleles

Filtering AF 0.069% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0628%

Overall 0.00464% 72/1,550,690 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0862%	1,160
Middle Eastern	0.0346%	2,888
Remaining individualsnot grpmax-eligible	0.00672%	14,885
Admixed American	0.00441%	22,654
South Asian	0.00244%	40,968

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.Val751Leu
Coding: c.2251G>C
MANE Select: NM_003198
dbSNP: rs145432831
Type: single nucleotide variant
Location: chr1:23757119 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 57.63 · 5 PDB

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-val751leu (accessed [today's date]).

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