Is ELL p.Ala72Thr (c.214G>A) pathogenic?

ELL p.Ala72Thr (c.214G>A) is classified Likely benign in ELL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely benign (0.0635); Very rare (popmax 0.00839%, eas).

How common is ELL p.Ala72Thr (c.214G>A) in the general population?

ELL p.Ala72Thr (c.214G>A) is very rare (popmax 0.00839%, eas) (gnomAD).

What do computational predictors say about ELL p.Ala72Thr (c.214G>A)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

ELL p.Ala72Thr

c.214G>A · rs771450349 · VCV3088308

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00839%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -5.89	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 -3.7	GERP -4.1
Regional constraint	o/e 0.92	unconstrained · MANE · 77 kb · p 0.013 · regional, not allelic
Overall
CADD	0.037	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 0.00839% East Asian · 3/35,768 alleles

Filtering AF 0.00222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00122%

Overall 0.00068% 9/1,323,950 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00839%	11,923
European (non-Finnish)	0.000583%	171,393

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.Ala72Thr
Coding: c.214G>A
MANE Select: NM_006532
dbSNP: rs771450349
Type: single nucleotide variant
Location: chr19:18465888 (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.Ala72Ser Uncertain significance ★ ⚠ same residue
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

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-ala72thr (accessed [today's date]).

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