Is ELL3 p.Arg35Pro (c.104G>C) pathogenic?

ELL3 p.Arg35Pro (c.104G>C) is classified Uncertain significance in ELL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely pathogenic (0.5655); Rare (popmax 0.345%, amr).

How common is ELL3 p.Arg35Pro (c.104G>C) in the general population?

ELL3 p.Arg35Pro (c.104G>C) is rare (popmax 0.345%, amr) (gnomAD).

What do computational predictors say about ELL3 p.Arg35Pro (c.104G>C)?

AlphaMissense predicts likely pathogenic (score 0.5655) — an in-silico prediction, not a clinical call.

ELL3 p.Arg35Pro

c.104G>C · VCV4248340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5655 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.345%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5655	likely pathogenic
REVEL	0.287	benign-leaning
SaProt	LLR -10.47	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 2.1	GERP 1.7, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 3,782 bp · p 0.35 · regional, not allelic
Overall
CADD	23.7	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

Grpmax group 0.345% Admixed American · 206/59,730 alleles

Filtering AF 0.306% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.291%

Overall 0.154% 2,480/1,609,836 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.345%	290
Middle Eastern	0.248%	403
European (non-Finnish)	0.18%	556
Remaining individualsnot grpmax-eligible	0.13%	768
Amishnot grpmax-eligible	0.11%	912
Ashkenazi Jewishnot grpmax-eligible	0.0747%	1,338
South Asian	0.0232%	4,316
African / African-American	0.0213%	4,687
Finnishnot grpmax-eligible	0.00315%	31,787

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.Arg35Pro
Coding: c.104G>C
MANE Select: NM_025165
Type: single nucleotide variant
Location: chr15:43776798 (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.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
ELL3 p.Arg212Cys 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-arg35pro (accessed [today's date]).

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