Is DONSON p.Arg211Cys (c.631C>T) pathogenic?

DONSON p.Arg211Cys (c.631C>T) is classified Pathogenic in DONSON (ClinVar, Single submitter, 2 submitters). AlphaMissense: ambiguous (0.3987); Very rare (popmax 0.00155%, nfe); Associated with Meier-Gorlin syndrome.

What condition is associated with DONSON p.Arg211Cys (c.631C>T)?

DONSON p.Arg211Cys (c.631C>T) is associated with Meier-Gorlin syndrome, Meier-Gorlin syndrome 10 (ClinVar).

How common is DONSON p.Arg211Cys (c.631C>T) in the general population?

DONSON p.Arg211Cys (c.631C>T) is very rare (popmax 0.00155%, nfe) (gnomAD).

What do computational predictors say about DONSON p.Arg211Cys (c.631C>T)?

AlphaMissense predicts ambiguous (score 0.3987) — an in-silico prediction, not a clinical call.

DONSON p.Arg211Cys

c.631C>T · rs774052186 · VCV1173053

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3987 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00155%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Meier-Gorlin syndrome

Computational evidence

Protein change
AlphaMissense	0.3987	ambiguous
REVEL	0.754	pathogenic-leaning
SaProt	LLR -8.62	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.34	loss · gain 0.13 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 8.7	GERP 5.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 10 kb · p 0.95 · regional, not allelic
Overall
CADD	33.0	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 0.00155% European (non-Finnish) · 18/1,159,926 alleles

Filtering AF 0.00097% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0008%

Overall 0.00126% 18/1,426,028 alleles · very rare

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.Arg211Cys
Coding: c.631C>T
MANE Select: NM_017613
dbSNP: rs774052186
Type: single nucleotide variant
Location: chr21:33584744 (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

Meier-Gorlin syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Meier-Gorlin syndrome 10

Similar variants

DONSON p.Arg211Gly Uncertain significance ★ ⚠ same residue
DONSON p.Arg211His Uncertain significance ★ same residue
DONSON p.Phe165Ser Pathogenic/Likely pathogenic ★★ same condition
DONSON c.607-36G>A Pathogenic ★ same condition
DONSON p.Pro545Leu Pathogenic ★ ⚠ same condition
DONSON p.Pro224Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
DONSON p.Tyr270Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
DONSON c.1047-9A>G 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-arg211cys (accessed [today's date]).

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