Is DONSON p.Arg319Thr (c.956G>C) pathogenic?

DONSON p.Arg319Thr (c.956G>C) is classified Uncertain significance in DONSON (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.2267); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with DONSON p.Arg319Thr (c.956G>C)?

DONSON p.Arg319Thr (c.956G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DONSON p.Arg319Thr (c.956G>C) in the general population?

DONSON p.Arg319Thr (c.956G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DONSON p.Arg319Thr (c.956G>C)?

AlphaMissense predicts likely benign (score 0.2267) — an in-silico prediction, not a clinical call.

DONSON p.Arg319Thr

c.956G>C · rs2086541100 · VCV2526462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2267 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2267	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -9.67	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 0.94	GERP 2.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 10 kb · p 0.95 · regional, not allelic
Overall
CADD	19.59	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 0.00223% East Asian · 1/44,842 alleles

Overall 0.000137% 2/1,461,326 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,842
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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: DONSON
Protein: p.Arg319Thr
Coding: c.956G>C
MANE Select: NM_017613
dbSNP: rs2086541100
Type: single nucleotide variant
Location: chr21:33583496 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.94
Residue 319: a UniProt-annotated variant site (in missla)

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.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
DONSON p.Arg234His Uncertain significance ★★ ⚠ same condition
DONSON p.Arg239Ser Uncertain significance ★★ ⚠ same condition
DONSON p.Arg29Cys 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-arg319thr (accessed [today's date]).

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