Is DND1 p.Pro128Ser (c.382C>T) pathogenic?

DND1 p.Pro128Ser (c.382C>T) is classified Uncertain significance in DND1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-05). AlphaMissense: likely benign (0.0905); Absent from gnomAD v4.1.

How common is DND1 p.Pro128Ser (c.382C>T) in the general population?

DND1 p.Pro128Ser (c.382C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DND1 p.Pro128Ser (c.382C>T)?

AlphaMissense predicts likely benign (score 0.0905) — an in-silico prediction, not a clinical call.

DND1 p.Pro128Ser

c.382C>T · rs1279936654 · VCV2609573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0905 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0905	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.47	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 9.6	GERP 1, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 919 bp · p 2e-08 · regional, not allelic
Overall
CADD	20.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DND1
Protein: p.Pro128Ser
Coding: c.382C>T
MANE Select: NM_194249
dbSNP: rs1279936654
Type: single nucleotide variant
Location: chr5:140672667 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 80.42 · 2 PDB
Residue 128: the rrm 1 domain

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-pro128ser (accessed [today's date]).

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