Is ELL2 p.Gln634Pro (c.1901A>C) pathogenic?

ELL2 p.Gln634Pro (c.1901A>C) is classified Uncertain significance in ELL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). AlphaMissense: likely pathogenic (0.6371); Absent from gnomAD v4.1.

How common is ELL2 p.Gln634Pro (c.1901A>C) in the general population?

ELL2 p.Gln634Pro (c.1901A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELL2 p.Gln634Pro (c.1901A>C)?

AlphaMissense predicts likely pathogenic (score 0.6371) — an in-silico prediction, not a clinical call.

ELL2 p.Gln634Pro

c.1901A>C · VCV3507947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6371 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6371	likely pathogenic
REVEL	0.154	moderately benign-leaning
SaProt	LLR -16.41	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 73 kb · p 8e-16 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELL2
Protein: p.Gln634Pro
Coding: c.1901A>C
MANE Select: NM_012081
Type: single nucleotide variant
Location: chr5:95888893 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.83 · 4 PDB
Residue 634: the ocel domain; an α-helix

Full ELL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELL2 p.Ile58Val Likely benign ★★ ⚠ same type
ELL2 p.Ala218Pro Uncertain significance ★ ⚠ same type
ELL2 p.Arg135Gln Uncertain significance ★ ⚠ same type
ELL2 p.Arg167Pro Uncertain significance ★ ⚠ same type
ELL2 p.Arg180Thr Uncertain significance ★ ⚠ same type
ELL2 p.Arg193Gln Uncertain significance ★ ⚠ same type
ELL2 p.Arg281Gln Uncertain significance ★ ⚠ same type
ELL2 p.Arg281Trp 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/ell2-p-gln634pro (accessed [today's date]).

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