Is SNCAIP p.Val224= (c.672C>T) pathogenic?

SNCAIP p.Val224= (c.672C>T) is classified Likely benign in SNCAIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-13). Ultra-rare (popmax 0.0987%, mid); Associated with Parkinson Disease, Dominant/Recessive.

What condition is associated with SNCAIP p.Val224= (c.672C>T)?

SNCAIP p.Val224= (c.672C>T) is associated with Parkinson Disease, Dominant/Recessive (ClinVar).

How common is SNCAIP p.Val224= (c.672C>T) in the general population?

SNCAIP p.Val224= (c.672C>T) is ultra-rare (popmax 0.0987%, mid) (gnomAD).

SNCAIP p.Val224=

c.672C>T · rs376151621 · VCV350489

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0987%, mid)

Conditions

Parkinson Disease, Dominant/Recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -5
Overall
CADD	0.415	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0987% Middle Eastern · 6/6,082 alleles

Filtering AF 0.0429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.0113% 182/1,613,650 alleles · ultra-rare exomes 165/1,461,482 · genomes 17/152,168 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0987%	1,014
Admixed American	0.0384%	2,607
Remaining individualsnot grpmax-eligible	0.0272%	3,675
European (non-Finnish)	0.0111%	9,006
African / African-American	0.00401%	24,963
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,590
Finnishnot grpmax-eligible	0.00156%	64,030

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.Val224=
Coding: c.672C>T
MANE Select: NM_005460
dbSNP: rs376151621
Type: single nucleotide variant
Location: chr5:122423409 (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-val224 (accessed [today's date]).

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