Is DNER p.Asn601Ile (c.1802A>T) pathogenic?

DNER p.Asn601Ile (c.1802A>T) is classified Uncertain significance in DNER (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: ambiguous (0.5161); Very rare (popmax 0.00161%, nfe).

How common is DNER p.Asn601Ile (c.1802A>T) in the general population?

DNER p.Asn601Ile (c.1802A>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about DNER p.Asn601Ile (c.1802A>T)?

AlphaMissense predicts ambiguous (score 0.5161) — an in-silico prediction, not a clinical call.

DNER p.Asn601Ile

c.1802A>T · VCV4243388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5161 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5161	ambiguous
REVEL	0.491	indeterminate
SaProt	LLR -15.63	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 1.8, phastCons 0.98
Regional constraint	o/e 0.94	unconstrained · MANE · 356 kb · p 0.066 · regional, not allelic
Overall
CADD	25.1	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 0.00161% European (non-Finnish) · 19/1,178,738 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000831%

Overall 0.00124% 20/1,611,602 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,039
Remaining individualsnot grpmax-eligible	0.0016%	62,392

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.Asn601Ile
Coding: c.1802A>T
MANE Select: NM_139072
Type: single nucleotide variant
Location: chr2:229388318 (GRCh38)
Gene constraint: LOEUF 0.561 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 70.51
Residue 601: the egf-like 10; calcium-binding domain; a disulfide bond

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-asn601ile (accessed [today's date]).

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