Is DND1 p.Arg287Cys (c.859C>T) pathogenic?

DND1 p.Arg287Cys (c.859C>T) is classified Uncertain significance in DND1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely benign (0.0753); Very rare (popmax 0.00531%, amr).

How common is DND1 p.Arg287Cys (c.859C>T) in the general population?

DND1 p.Arg287Cys (c.859C>T) is very rare (popmax 0.00531%, amr) (gnomAD).

What do computational predictors say about DND1 p.Arg287Cys (c.859C>T)?

AlphaMissense predicts likely benign (score 0.0753) — an in-silico prediction, not a clinical call.

DND1 p.Arg287Cys

c.859C>T · VCV3841630

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0753 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00531%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0753	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -7.17	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 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 1,240 bp · p 0.00011 · regional, not allelic
Overall
CADD	25.6	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 0.00531% Admixed American · 3/56,526 alleles

Filtering AF 0.00344% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.0037% 59/1,595,770 alleles · very rare exomes 56/1,443,556 · genomes 3/152,214 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00531%	18,842
European (non-Finnish)	0.00443%	22,557
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,240
Remaining individualsnot grpmax-eligible	0.00324%	30,845
South Asian	0.00112%	89,404

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: DND1
Protein: p.Arg287Cys
Coding: c.859C>T
MANE Select: NM_194249
Type: single nucleotide variant
Location: chr5:140671496 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 80.42 · 2 PDB

Full DND1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DND1 p.Ala157Val Uncertain significance ★ ⚠ same type
DND1 p.Ala177Val Uncertain significance ★ ⚠ same type
DND1 p.Ala182Val Uncertain significance ★ ⚠ same type
DND1 p.Ala195Thr Uncertain significance ★ same type
DND1 p.Ala20Thr Uncertain significance ★ ⚠ same type
DND1 p.Ala244Pro Uncertain significance ★ ⚠ same type
DND1 p.Ala345Val Uncertain significance ★ ⚠ same type
DND1 p.Arg13Lys 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/dnd1-p-arg287cys (accessed [today's date]).

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