Is ELL p.Pro66Ser (c.196C>T) pathogenic?

ELL p.Pro66Ser (c.196C>T) is classified Uncertain significance in ELL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely pathogenic (0.6923); Absent from gnomAD v4.1.

How common is ELL p.Pro66Ser (c.196C>T) in the general population?

ELL p.Pro66Ser (c.196C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELL p.Pro66Ser (c.196C>T)?

AlphaMissense predicts likely pathogenic (score 0.6923) — an in-silico prediction, not a clinical call.

ELL p.Pro66Ser

c.196C>T · VCV4248307

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6923 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,324,858)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6923	likely pathogenic
REVEL	0.567	indeterminate
SaProt	LLR -13.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 77 kb · p 0.013 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,324,858). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ELL
Protein: p.Pro66Ser
Coding: c.196C>T
MANE Select: NM_006532
Type: single nucleotide variant
Location: chr19:18465906 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.31 · 1 PDB

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-pro66ser (accessed [today's date]).

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