Is SNCAIP p.Pro212= (c.636C>T) pathogenic?

SNCAIP p.Pro212= (c.636C>T) is classified Benign/Likely benign in SNCAIP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-15). Rare (popmax 0.104%, nfe); Associated with Parkinson Disease, Dominant/Recessive.

What condition is associated with SNCAIP p.Pro212= (c.636C>T)?

SNCAIP p.Pro212= (c.636C>T) is associated with Parkinson Disease, Dominant/Recessive (ClinVar).

How common is SNCAIP p.Pro212= (c.636C>T) in the general population?

SNCAIP p.Pro212= (c.636C>T) is rare (popmax 0.104%, nfe) (gnomAD).

SNCAIP p.Pro212=

c.636C>T · rs56331004 · VCV350487

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.104%, nfe)

Conditions

Parkinson Disease, Dominant/Recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.9	GERP -5.1
Overall
CADD	0.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.104% European (non-Finnish) · 1,231/1,179,650 alleles

Filtering AF 0.0995% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0975%

Overall 0.12% 1,930/1,613,544 alleles · rare exomes 1,640/1,461,272 · genomes 290/152,272 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.877%	114
Finnishnot grpmax-eligible	0.678%	148
Ashkenazi Jewishnot grpmax-eligible	0.51%	196
Remaining individualsnot grpmax-eligible	0.114%	880
European (non-Finnish)grpmax	0.104%	958
South Asian	0.022%	4,554
Middle Eastern	0.0165%	6,060
Admixed American	0.0133%	7,493
African / African-American	0.00801%	12,489

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SNCAIP
Protein: p.Pro212=
Coding: c.636C>T
MANE Select: NM_005460
dbSNP: rs56331004
Type: single nucleotide variant
Location: chr5:122423373 (GRCh38)
Gene constraint: LOEUF 0.636 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.98 · 1 PDB

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

Disease context

Parkinson Disease, Dominant/Recessive

Similar variants

SNCAIP p.Ala363Thr Uncertain significance ★★ ⚠ same condition
SNCAIP p.Glu237Lys Uncertain significance ★★ ⚠ same condition
SNCAIP p.Leu148= Uncertain significance ★★ same condition
SNCAIP p.Ser912Arg Uncertain significance ★★ ⚠ same condition
SNCAIP c.*103C>T Likely benign ★★ same condition
SNCAIP c.*46T>G Likely benign ★★ same condition
SNCAIP c.*70C>G Benign/Likely benign ★★ same condition
SNCAIP p.Arg621Cys Likely benign ★★ 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/sncaip-p-pro212 (accessed [today's date]).

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