Is DNER p.Ala362Val (c.1085C>T) pathogenic?

DNER p.Ala362Val (c.1085C>T) is classified Uncertain significance in DNER (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-16). AlphaMissense: likely pathogenic (0.6772); Very rare (popmax 0.00373%, nfe).

How common is DNER p.Ala362Val (c.1085C>T) in the general population?

DNER p.Ala362Val (c.1085C>T) is very rare (popmax 0.00373%, nfe) (gnomAD).

What do computational predictors say about DNER p.Ala362Val (c.1085C>T)?

AlphaMissense predicts likely pathogenic (score 0.6772) — an in-silico prediction, not a clinical call.

DNER p.Ala362Val

c.1085C>T · rs369585918 · VCV3084650

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6772 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6772	likely pathogenic
REVEL	0.472	indeterminate
SaProt	LLR -15.92	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -0.67, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 356 kb · p 0.066 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00373% European (non-Finnish) · 44/1,180,004 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00304% 49/1,614,062 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00373%	26,818
South Asian	0.00329%	30,358
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,004

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.Ala362Val
Coding: c.1085C>T
MANE Select: NM_139072
dbSNP: rs369585918
Type: single nucleotide variant
Location: chr2:229512845 (GRCh38)
Gene constraint: LOEUF 0.561 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 70.51
Residue 362: a disulfide bond; the egf-like 4 domain

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

Similar variants

DNER p.Ala362Thr Uncertain significance ★ ⚠ same residue
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

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-ala362val (accessed [today's date]).

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