Is SNCAIP p.Ser200Pro (c.598T>C) pathogenic?

SNCAIP p.Ser200Pro (c.598T>C) is classified Uncertain significance in SNCAIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-06). AlphaMissense: likely benign (0.0725); Very rare (popmax 0.00668%, eas).

How common is SNCAIP p.Ser200Pro (c.598T>C) in the general population?

SNCAIP p.Ser200Pro (c.598T>C) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about SNCAIP p.Ser200Pro (c.598T>C)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

SNCAIP p.Ser200Pro

c.598T>C · VCV3321157

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -8.01	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 -0.27	GERP -4.3
Regional constraint	o/e 0.89	unconstrained · MANE · 72 kb · p 0.00024 · regional, not allelic
Overall
CADD	11.77	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 0.00668% East Asian · 3/44,892 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000929% 15/1,613,940 alleles · very rare exomes 14/1,461,788 · genomes 1/152,152 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,964
Admixed American	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00134%	74,870
European (non-Finnish)	0.000593%	168,570

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.Ser200Pro
Coding: c.598T>C
MANE Select: NM_005460
Type: single nucleotide variant
Location: chr5:122423335 (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

Similar variants

SNCAIP p.Ala358Val Uncertain significance ★★ ⚠ same type
SNCAIP p.Ala363Thr Uncertain significance ★★ ⚠ same type
SNCAIP p.Glu237Lys Uncertain significance ★★ ⚠ same type
SNCAIP p.Leu148= Uncertain significance ★★ same type
SNCAIP p.Ser912Arg Uncertain significance ★★ ⚠ same type
SNCAIP p.Val461Ile Uncertain significance ★★ ⚠ same type
SNCAIP c.*103C>T Likely benign ★★ same type
SNCAIP c.*46T>G Likely benign ★★ 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/sncaip-p-ser200pro (accessed [today's date]).

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