Is ELL2 p.Arg167Pro (c.500G>C) pathogenic?

ELL2 p.Arg167Pro (c.500G>C) is classified Uncertain significance in ELL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely pathogenic (0.9278); Very rare (popmax 0.00492%, nfe).

How common is ELL2 p.Arg167Pro (c.500G>C) in the general population?

ELL2 p.Arg167Pro (c.500G>C) is very rare (popmax 0.00492%, nfe) (gnomAD).

What do computational predictors say about ELL2 p.Arg167Pro (c.500G>C)?

AlphaMissense predicts likely pathogenic (score 0.9278) — an in-silico prediction, not a clinical call.

ELL2 p.Arg167Pro

c.500G>C · rs572461947 · VCV2206461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9278 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9278	likely pathogenic
REVEL	0.357	indeterminate
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 73 kb · p 8e-16 · regional, not allelic
Overall
CADD	29.1	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 0.00492% European (non-Finnish) · 58/1,177,998 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00366% 59/1,610,698 alleles · very rare exomes 56/1,458,668 · genomes 3/152,030 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00492%	20,310
Remaining individualsnot grpmax-eligible	0.0016%	62,332

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: ELL2
Protein: p.Arg167Pro
Coding: c.500G>C
MANE Select: NM_012081
dbSNP: rs572461947
Type: single nucleotide variant
Location: chr5:95906764 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.83 · 4 PDB

Full ELL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELL2 p.Ile58Val Likely benign ★★ same type
ELL2 p.Ala218Pro Uncertain significance ★ ⚠ same type
ELL2 p.Arg135Gln Uncertain significance ★ ⚠ same type
ELL2 p.Arg180Thr Uncertain significance ★ ⚠ same type
ELL2 p.Arg193Gln Uncertain significance ★ ⚠ same type
ELL2 p.Arg281Gln Uncertain significance ★ ⚠ same type
ELL2 p.Arg281Trp Uncertain significance ★ ⚠ same type
ELL2 p.Arg302Cys 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/ell2-p-arg167pro (accessed [today's date]).

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