Is ELL p.Leu427= (c.1279C>T) pathogenic?

ELL p.Leu427= (c.1279C>T) is classified Benign in ELL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-07-22). Common (popmax 6.78%, afr) — too common for a highly-penetrant pathogenic allele.

ELL p.Leu427=

Q: How common is ELL p.Leu427= (c.1279C>T) in the general population?

ELL p.Leu427= (c.1279C>T) is common (popmax 6.78%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1279C>T · rs34868531 · VCV1304815

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.78%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -3.8, phastCons 0.92
Overall
CADD	3.375	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.78% African / African-American · 5,068/74,724 alleles

Filtering AF 6.63% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.56%

Overall 1% 15,961/1,591,648 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.78%	15
Middle Eastern	1.19%	84
Remaining individualsnot grpmax-eligible	1.13%	89
Admixed American	0.947%	106
European (non-Finnish)	0.763%	131
Ashkenazi Jewishnot grpmax-eligible	0.748%	134
Finnishnot grpmax-eligible	0.68%	147
South Asian	0.0516%	1,939

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: ELL
Protein: p.Leu427=
Coding: c.1279C>T
MANE Select: NM_006532
dbSNP: rs34868531
Type: single nucleotide variant
Location: chr19:18450663 (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.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
ELL p.Ala43Val 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-leu427 (accessed [today's date]).

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