Is DSN1 p.Ser95Pro (c.283T>C) pathogenic?

DSN1 p.Ser95Pro (c.283T>C) is classified Uncertain significance in DSN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). AlphaMissense: likely pathogenic (0.6761); Absent from gnomAD v4.1.

How common is DSN1 p.Ser95Pro (c.283T>C) in the general population?

DSN1 p.Ser95Pro (c.283T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSN1 p.Ser95Pro (c.283T>C)?

AlphaMissense predicts likely pathogenic (score 0.6761) — an in-silico prediction, not a clinical call.

DSN1 p.Ser95Pro

c.283T>C · rs2518726573 · VCV2527789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6761 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6761	likely pathogenic · top 9% in DSN1
REVEL	0.503	indeterminate
SaProt	LLR -10.67	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.32 · regional, not allelic
Overall
CADD	27.3	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

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: DSN1
Protein: p.Ser95Pro
Coding: c.283T>C
MANE Select: NM_001145315
dbSNP: rs2518726573
Type: single nucleotide variant
Location: chr20:36770945 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.28 · 5 PDB

Full DSN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSN1 p.Ser95Phe Uncertain significance ★ ⚠ same residue
DSN1 p.Gln24= Benign ★★ same type
DSN1 p.Arg106Gln Uncertain significance ★ ⚠ same type
DSN1 p.Arg107Gln Uncertain significance ★ ⚠ same type
DSN1 p.Arg122Gln Uncertain significance ★ ⚠ same type
DSN1 p.Arg97Trp Uncertain significance ★ ⚠ same type
DSN1 p.Asp127His Uncertain significance ★ ⚠ same type
DSN1 p.Asp273Ala 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/dsn1-p-ser95pro (accessed [today's date]).

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