Is DNER p.Arg698Gln (c.2093G>A) pathogenic?

DNER p.Arg698Gln (c.2093G>A) is classified Uncertain significance in DNER (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: ambiguous (0.4069); Very rare (popmax 0.00364%, nfe).

How common is DNER p.Arg698Gln (c.2093G>A) in the general population?

DNER p.Arg698Gln (c.2093G>A) is very rare (popmax 0.00364%, nfe) (gnomAD).

What do computational predictors say about DNER p.Arg698Gln (c.2093G>A)?

AlphaMissense predicts ambiguous (score 0.4069) — an in-silico prediction, not a clinical call.

DNER p.Arg698Gln

c.2093G>A · rs143853534 · VCV2378643

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4069 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4069	ambiguous
REVEL	0.567	indeterminate
SaProt	LLR -7.39	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 356 kb · p 0.066 · regional, not allelic
Overall
CADD	33.0	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 0.00364% European (non-Finnish) · 43/1,180,034 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00279% 45/1,613,998 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,443
Remaining individualsnot grpmax-eligible	0.0032%	31,240

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: DNER
Protein: p.Arg698Gln
Coding: c.2093G>A
MANE Select: NM_139072
dbSNP: rs143853534
Type: single nucleotide variant
Location: chr2:229366882 (GRCh38)
Gene constraint: LOEUF 0.561 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 70.51

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

Similar variants

DNER p.Arg698= Benign ★★ same residue
DNER c.586-10C>T Benign ★★ same type
DNER p.Pro180= Benign ★★ same type
DNER p.Thr142Ile Benign ★★ ⚠ same type
DNER p.Ala11Val Uncertain significance ★ ⚠ same type
DNER p.Ala171Thr Uncertain significance ★ ⚠ same type
DNER p.Ala205Thr Uncertain significance ★ ⚠ same type
DNER p.Ala234Thr 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/dner-p-arg698gln (accessed [today's date]).

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