Is ELL3 p.Ser84Arg (c.252C>A) pathogenic?

ELL3 p.Ser84Arg (c.252C>A) is classified Uncertain significance in ELL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). AlphaMissense: ambiguous (0.3544); Absent from gnomAD v4.1.

How common is ELL3 p.Ser84Arg (c.252C>A) in the general population?

ELL3 p.Ser84Arg (c.252C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELL3 p.Ser84Arg (c.252C>A)?

AlphaMissense predicts ambiguous (score 0.3544) — an in-silico prediction, not a clinical call.

ELL3 p.Ser84Arg

c.252C>A · VCV3507956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3544 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3544	ambiguous
REVEL	0.215	benign-leaning
SaProt	LLR -6.41	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.2	GERP -0.56, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 3,782 bp · p 0.35 · regional, not allelic
Overall
CADD	19.77	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: ELL3
Protein: p.Ser84Arg
Coding: c.252C>A
MANE Select: NM_025165
Type: single nucleotide variant
Location: chr15:43776068 (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-ser84arg (accessed [today's date]).

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