Is SNCAIP p.Ser716= (c.2148C>T) pathogenic?

SNCAIP p.Ser716= (c.2148C>T) is classified Likely benign in SNCAIP (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0156%, eas); Associated with Parkinson Disease, Dominant/Recessive.

What condition is associated with SNCAIP p.Ser716= (c.2148C>T)?

SNCAIP p.Ser716= (c.2148C>T) is associated with Parkinson Disease, Dominant/Recessive (ClinVar).

How common is SNCAIP p.Ser716= (c.2148C>T) in the general population?

SNCAIP p.Ser716= (c.2148C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

SNCAIP p.Ser716=

c.2148C>T · rs536468779 · VCV350501

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

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 1.8	GERP 1.3, phastCons 1
Overall
CADD	4.271	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,886 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.000991% 16/1,614,124 alleles · ultra-rare exomes 14/1,461,866 · genomes 2/152,258 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,412
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	8.47e-05%	1,180,020

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.Ser716=
Coding: c.2148C>T
MANE Select: NM_005460
dbSNP: rs536468779
Type: single nucleotide variant
Location: chr5:122450995 (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.Ser716Asn Uncertain significance ★ ⚠ same residue
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

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-ser716 (accessed [today's date]).

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