Is SPIN2A p.Arg47Ser (c.141G>T) pathogenic?

SPIN2A p.Arg47Ser (c.141G>T) is classified Uncertain significance in SPIN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-24). AlphaMissense: likely benign (0.2539); Very rare (popmax 0.00386%, afr).

How common is SPIN2A p.Arg47Ser (c.141G>T) in the general population?

SPIN2A p.Arg47Ser (c.141G>T) is very rare (popmax 0.00386%, afr) (gnomAD).

What do computational predictors say about SPIN2A p.Arg47Ser (c.141G>T)?

AlphaMissense predicts likely benign (score 0.2539) — an in-silico prediction, not a clinical call.

SPIN2A p.Arg47Ser

c.141G>T · rs996692168 · VCV2472549

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2539 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00386%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2539	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -4.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.4
Regional constraint	o/e 0.23	constrained · MANE · 383 bp · p 5e-11 · regional, not allelic
Overall
CADD	18.96	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

Grpmax group 0.00386% African / African-American · 1/25,926 alleles

Filtering AF 0.000885% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000567%

Overall 0.0016% 10/623,919 alleles · very rare exomes 9/579,054 · genomes 1/44,865 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00386%	25,926
Remaining individualsnot grpmax-eligible	0.00348%	28,716
European (non-Finnish)	0.00183%	54,747

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: SPIN2A
Protein: p.Arg47Ser
Coding: c.141G>T
MANE Select: NM_019003
dbSNP: rs996692168
Type: single nucleotide variant
Location: chrX:57136457 (GRCh38)
Structure: AlphaFold pLDDT 81.67
Residue 47: the 'disordered' region

Full SPIN2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SPIN2A p.Ala155Pro Uncertain significance ★ ⚠ same type
SPIN2A p.Arg113Thr Uncertain significance ★ ⚠ same type
SPIN2A p.Arg187Cys Uncertain significance ★ ⚠ same type
SPIN2A p.Arg38Lys Uncertain significance ★ ⚠ same type
SPIN2A p.Asp180Gly Uncertain significance ★ ⚠ same type
SPIN2A p.Asp253His Uncertain significance ★ ⚠ same type
SPIN2A p.Glu138Gln Uncertain significance ★ same type
SPIN2A p.Glu199Asp Uncertain significance ★ ⚠ 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/spin2a-p-arg47ser (accessed [today's date]).

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