Is DONSON p.Ala183Ser (c.547G>T) pathogenic?

DONSON p.Ala183Ser (c.547G>T) is classified Conflicting classifications of pathogenicity in DONSON (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1758); Ultra-rare (popmax 0.0457%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DONSON p.Ala183Ser (c.547G>T)?

DONSON p.Ala183Ser (c.547G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DONSON p.Ala183Ser (c.547G>T) in the general population?

DONSON p.Ala183Ser (c.547G>T) is ultra-rare (popmax 0.0457%, nfe) (gnomAD).

What do computational predictors say about DONSON p.Ala183Ser (c.547G>T)?

AlphaMissense predicts likely benign (score 0.1758) — an in-silico prediction, not a clinical call.

DONSON p.Ala183Ser

c.547G>T · rs147415181 · VCV1354046

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1758 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0457%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1758	likely benign
REVEL	0.569	indeterminate
SaProt	LLR -8.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 5.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 10 kb · p 0.95 · regional, not allelic
Overall
CADD	23.9	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 0.0457% European (non-Finnish) · 539/1,180,032 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0412%

Overall 0.0373% 602/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0457%	2,189
Remaining individualsnot grpmax-eligible	0.04%	2,500
Admixed American	0.0333%	3,000
Middle Eastern	0.0329%	3,042
African / African-American	0.0147%	6,812
Finnishnot grpmax-eligible	0.00781%	12,805

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.Ala183Ser
Coding: c.547G>T
MANE Select: NM_017613
dbSNP: rs147415181
Type: single nucleotide variant
Location: chr21:33586037 (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.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-ala183ser (accessed [today's date]).

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