Is DONSON p.His482Tyr (c.1444C>T) pathogenic?

DONSON p.His482Tyr (c.1444C>T) is classified Conflicting classifications of pathogenicity in DONSON (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-28). AlphaMissense: likely benign (0.0974); Rare (popmax 0.132%, sas); Associated with Inborn genetic diseases.

What condition is associated with DONSON p.His482Tyr (c.1444C>T)?

DONSON p.His482Tyr (c.1444C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DONSON p.His482Tyr (c.1444C>T) in the general population?

DONSON p.His482Tyr (c.1444C>T) is rare (popmax 0.132%, sas) (gnomAD).

What do computational predictors say about DONSON p.His482Tyr (c.1444C>T)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

DONSON p.His482Tyr

c.1444C>T · rs544638959 · VCV1520431

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -6.93	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 6.8	GERP 4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 10 kb · p 0.95 · regional, not allelic
Overall
CADD	20.6	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

Grpmax group 0.132% South Asian · 120/91,088 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.105%

Overall 0.00843% 136/1,614,240 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.132%	759
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Admixed American	0.00333%	30,017
Finnishnot grpmax-eligible	0.00156%	64,042
African / African-American	0.00133%	75,076
European (non-Finnish)	8.47e-05%	1,180,027

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.His482Tyr
Coding: c.1444C>T
MANE Select: NM_017613
dbSNP: rs544638959
Type: single nucleotide variant
Location: chr21:33579469 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.94
Residue 482: 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.His482Arg Uncertain significance ★ ⚠ 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
DONSON p.Arg234His Uncertain significance ★★ ⚠ same condition
DONSON p.Arg239Ser 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-his482tyr (accessed [today's date]).

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