Is ELL2 p.Gln235Pro (c.704A>C) pathogenic?

ELL2 p.Gln235Pro (c.704A>C) is classified Uncertain significance in ELL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-27). AlphaMissense: likely benign (0.0745); Rare (popmax 0.281%, mid).

How common is ELL2 p.Gln235Pro (c.704A>C) in the general population?

ELL2 p.Gln235Pro (c.704A>C) is rare (popmax 0.281%, mid) (gnomAD).

What do computational predictors say about ELL2 p.Gln235Pro (c.704A>C)?

AlphaMissense predicts likely benign (score 0.0745) — an in-silico prediction, not a clinical call.

ELL2 p.Gln235Pro

c.704A>C · rs773358086 · VCV2602254

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0745 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.281%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0745	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -9.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 73 kb · p 8e-16 · regional, not allelic
Overall
CADD	24.2	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 0.281% Middle Eastern · 17/6,058 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.00397% 64/1,613,802 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.281%	356
South Asian	0.0505%	1,979
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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: ELL2
Protein: p.Gln235Pro
Coding: c.704A>C
MANE Select: NM_012081
dbSNP: rs773358086
Type: single nucleotide variant
Location: chr5:95906560 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.83 · 4 PDB
Residue 235: 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-gln235pro (accessed [today's date]).

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