Is ELL3 p.Val45Ile (c.133G>A) pathogenic?

ELL3 p.Val45Ile (c.133G>A) is classified Uncertain significance in ELL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.1323); Ultra-rare (popmax 0.0497%, mid).

How common is ELL3 p.Val45Ile (c.133G>A) in the general population?

ELL3 p.Val45Ile (c.133G>A) is ultra-rare (popmax 0.0497%, mid) (gnomAD).

What do computational predictors say about ELL3 p.Val45Ile (c.133G>A)?

AlphaMissense predicts likely benign (score 0.1323) — an in-silico prediction, not a clinical call.

ELL3 p.Val45Ile

c.133G>A · rs201169965 · VCV2384473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1323 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0497%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1323	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.38	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.8	GERP 0.57, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 3,782 bp · p 0.35 · regional, not allelic
Overall
CADD	23.3	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0497% Middle Eastern · 3/6,032 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00789%

Overall 0.00421% 66/1,567,572 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0497%	2,011
Finnishnot grpmax-eligible	0.0462%	2,163
South Asian	0.0163%	6,121
European (non-Finnish)	0.00173%	57,731
Remaining individualsnot grpmax-eligible	0.00165%	60,666

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: ELL3
Protein: p.Val45Ile
Coding: c.133G>A
MANE Select: NM_025165
dbSNP: rs201169965
Type: single nucleotide variant
Location: chr15:43776544 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.88

Full ELL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELL3 p.Val45Leu Uncertain significance ★ ⚠ same residue
ELL3 p.Ala134Gly Uncertain significance ★ ⚠ same type
ELL3 p.Ala185Thr Uncertain significance ★ ⚠ same type
ELL3 p.Ala203Glu Uncertain significance ★ ⚠ same type
ELL3 p.Ala203Pro Uncertain significance ★ ⚠ same type
ELL3 p.Ala297Thr Uncertain significance ★ ⚠ same type
ELL3 p.Ala312Gly Uncertain significance ★ ⚠ same type
ELL3 p.Arg109His 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/ell3-p-val45ile (accessed [today's date]).

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