Is DONSON p.Arg211His (c.632G>A) pathogenic?

DONSON p.Arg211His (c.632G>A) is classified Uncertain significance in DONSON (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-14). AlphaMissense: ambiguous (0.4318); Very rare (popmax 0.00134%, afr).

How common is DONSON p.Arg211His (c.632G>A) in the general population?

DONSON p.Arg211His (c.632G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about DONSON p.Arg211His (c.632G>A)?

AlphaMissense predicts ambiguous (score 0.4318) — an in-silico prediction, not a clinical call.

DONSON p.Arg211His

c.632G>A · rs1042218992 · VCV1950896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4318 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
AlphaMissense	0.4318	ambiguous
REVEL	0.384	indeterminate
SaProt	LLR -7.72	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 5.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 10 kb · p 0.95 · regional, not allelic
Overall
CADD	31.0	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 0.00134% African / African-American · 1/74,436 alleles

Filtering AF 0.000249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00016%

Overall 0.000501% 8/1,596,568 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,436
European (non-Finnish)	0.000598%	167,091

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.Arg211His
Coding: c.632G>A
MANE Select: NM_017613
dbSNP: rs1042218992
Type: single nucleotide variant
Location: chr21:33584743 (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

Similar variants

DONSON p.Arg211Cys Pathogenic ★ ⚠ same residue
DONSON p.Arg211Gly 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-arg211his (accessed [today's date]).

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