Is ELL p.Val25Met (c.73G>A) pathogenic?

ELL p.Val25Met (c.73G>A) is classified Uncertain significance in ELL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely pathogenic (0.6654); Very rare (popmax 0.00167%, amr).

How common is ELL p.Val25Met (c.73G>A) in the general population?

ELL p.Val25Met (c.73G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ELL p.Val25Met (c.73G>A)?

AlphaMissense predicts likely pathogenic (score 0.6654) — an in-silico prediction, not a clinical call.

ELL p.Val25Met

c.73G>A · VCV4248310

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6654	likely pathogenic
REVEL	0.281	benign-leaning
SaProt	LLR -7.83	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 77 kb · p 0.013 · regional, not allelic
Overall
CADD	24.5	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 0.00167% Admixed American · 1/59,922 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,611,384 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,922
Finnishnot grpmax-eligible	0.00157%	63,732
European (non-Finnish)	0.000254%	392,983

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.Val25Met
Coding: c.73G>A
MANE Select: NM_006532
Type: single nucleotide variant
Location: chr19:18521983 (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-val25met (accessed [today's date]).

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