Is DONSON p.Ser344Arg (c.1032C>A) pathogenic?

DONSON p.Ser344Arg (c.1032C>A) is classified Uncertain significance in DONSON (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-24). AlphaMissense: likely benign (0.1847); Absent from gnomAD v4.1.

How common is DONSON p.Ser344Arg (c.1032C>A) in the general population?

DONSON p.Ser344Arg (c.1032C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DONSON p.Ser344Arg (c.1032C>A)?

AlphaMissense predicts likely benign (score 0.1847) — an in-silico prediction, not a clinical call.

DONSON p.Ser344Arg

c.1032C>A · VCV4847716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1847 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1847	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.75 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.5	GERP 4, phastCons 0.98
Regional constraint	o/e 1.00	unconstrained · MANE · 10 kb · p 0.95 · regional, not allelic
Overall
CADD	17.54	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

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.Ser344Arg
Coding: c.1032C>A
MANE Select: NM_017613
Type: single nucleotide variant
Location: chr21:33582179 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.94
Residue 344: a UniProt-annotated variant site (in missla)

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

Similar variants

DONSON p.Ser344Thr Uncertain significance ★★ ⚠ same residue
DONSON p.Ser344= Uncertain significance ★ same residue
DONSON c.1047-9A>G Pathogenic ★★ same type
DONSON c.1563+1G>T Pathogenic ★★ same type
DONSON p.Arg293Ter Pathogenic ★★ same type
DONSON p.Arg442Ter Pathogenic ★★ same type
DONSON p.Gln428Ter Pathogenic/Likely pathogenic ★★ same type
DONSON p.Phe165Ser Pathogenic/Likely pathogenic ★★ 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/donson-p-ser344arg (accessed [today's date]).

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