Is ELL p.Gln435Arg (c.1304A>G) pathogenic?

ELL p.Gln435Arg (c.1304A>G) is classified Uncertain significance in ELL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely benign (0.0712); Very rare (popmax 8.5e-05%, nfe).

How common is ELL p.Gln435Arg (c.1304A>G) in the general population?

ELL p.Gln435Arg (c.1304A>G) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about ELL p.Gln435Arg (c.1304A>G)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

ELL p.Gln435Arg

c.1304A>G · VCV3844439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -6.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1	GERP 0.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 77 kb · p 0.013 · regional, not allelic
Overall
CADD	15.11	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 8.5e-05% European (non-Finnish) · 1/1,177,062 alleles

Overall 6.88e-05% 1/1,453,996 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: ELL
Protein: p.Gln435Arg
Coding: c.1304A>G
MANE Select: NM_006532
Type: single nucleotide variant
Location: chr19:18450638 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.31 · 1 PDB
Residue 435: the 'disordered' region

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

Similar variants

ELL p.Leu427= Benign ★★ same type
ELL p.Ser297Asn Benign ★★ same type
ELL p.Ala172Val Uncertain significance ★ ⚠ same type
ELL p.Ala237Gly Uncertain significance ★ ⚠ same type
ELL p.Ala237Val Uncertain significance ★ ⚠ same type
ELL p.Ala241Val Uncertain significance ★ ⚠ same type
ELL p.Ala348Val Uncertain significance ★ ⚠ same type
ELL p.Ala420Thr 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/ell-p-gln435arg (accessed [today's date]).

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