Is DNER p.Gln68Arg (c.203A>G) pathogenic?

DNER p.Gln68Arg (c.203A>G) is classified Uncertain significance in DNER (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.0798); Ultra-rare (popmax 0.0285%, afr).

How common is DNER p.Gln68Arg (c.203A>G) in the general population?

DNER p.Gln68Arg (c.203A>G) is ultra-rare (popmax 0.0285%, afr) (gnomAD).

What do computational predictors say about DNER p.Gln68Arg (c.203A>G)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

DNER p.Gln68Arg

c.203A>G · VCV4661463

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -6.23	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 2.3	GERP 0.37, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 356 kb · p 0.066 · regional, not allelic
Overall
CADD	9.71	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0285% African / African-American · 19/66,574 alleles

Filtering AF 0.0186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0155%

Overall 0.00158% 22/1,396,254 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0285%	3,504
Admixed American	0.00604%	16,544
Remaining individualsnot grpmax-eligible	0.00189%	53,016

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.Gln68Arg
Coding: c.203A>G
MANE Select: NM_139072
Type: single nucleotide variant
Location: chr2:229714221 (GRCh38)
Gene constraint: LOEUF 0.561 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 70.51
Residue 68: the 'interaction with notch1' region; a disulfide bond; the egf-like 1 domain

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

Similar variants

DNER c.586-10C>T Benign ★★ same type
DNER p.Arg698= 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-gln68arg (accessed [today's date]).

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