Is DONSON p.Thr161Pro (c.481A>C) pathogenic?

DONSON p.Thr161Pro (c.481A>C) is classified Uncertain significance in DONSON (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: ambiguous (0.4995); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DONSON p.Thr161Pro (c.481A>C)?

DONSON p.Thr161Pro (c.481A>C) is associated with Inborn genetic diseases (ClinVar).

How common is DONSON p.Thr161Pro (c.481A>C) in the general population?

DONSON p.Thr161Pro (c.481A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DONSON p.Thr161Pro (c.481A>C)?

AlphaMissense predicts ambiguous (score 0.4995) — an in-silico prediction, not a clinical call.

DONSON p.Thr161Pro

c.481A>C · rs2517479875 · VCV2260747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4995	ambiguous
REVEL	0.737	pathogenic-leaning
SaProt	LLR -13.70	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 4.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 10 kb · p 0.95 · regional, not allelic
Overall
CADD	26.3	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

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: DONSON
Protein: p.Thr161Pro
Coding: c.481A>C
MANE Select: NM_017613
dbSNP: rs2517479875
Type: single nucleotide variant
Location: chr21:33586103 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.94

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DONSON p.Thr161Ser Uncertain significance ★ ⚠ same residue
DONSON p.Thr161Met Uncertain significance ★★ ⚠ same residue
DONSON p.Thr161= Likely benign ★ same residue
DONSON p.Arg442Ter Pathogenic ★★ same condition
DONSON p.Gln428Ter Pathogenic/Likely pathogenic ★★ same condition
DONSON p.Ala32Gly Uncertain significance ★★ ⚠ same condition
DONSON p.Ala429Glu Uncertain significance ★★ ⚠ same condition
DONSON p.Arg162Gln Uncertain significance ★★ ⚠ same condition

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/donson-p-thr161pro (accessed [today's date]).

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