Is SCAMP2 p.Pro196Ser (c.586C>T) pathogenic?

SCAMP2 p.Pro196Ser (c.586C>T) is classified Uncertain significance in SCAMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-28). AlphaMissense: likely pathogenic (0.7937); Ultra-rare (popmax 0.02%, afr).

How common is SCAMP2 p.Pro196Ser (c.586C>T) in the general population?

SCAMP2 p.Pro196Ser (c.586C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about SCAMP2 p.Pro196Ser (c.586C>T)?

AlphaMissense predicts likely pathogenic (score 0.7937) — an in-silico prediction, not a clinical call.

SCAMP2 p.Pro196Ser

c.586C>T · VCV3792926

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7937 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7937	likely pathogenic
REVEL	0.629	indeterminate
SaProt	LLR -11.18	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 28 kb · p 0.0057 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.02% African / African-American · 15/74,924 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00989%

Overall 0.00118% 19/1,614,030 alleles · ultra-rare exomes 12/1,461,828 · genomes 7/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,995
Admixed American	0.005%	20,003
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: SCAMP2
Protein: p.Pro196Ser
Coding: c.586C>T
MANE Select: NM_005697
Type: single nucleotide variant
Location: chr15:74850560 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.30

Full SCAMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCAMP2 p.Ala143Pro Uncertain significance ★ ⚠ same type
SCAMP2 p.Ala295Val Uncertain significance ★ ⚠ same type
SCAMP2 p.Ala325Thr Uncertain significance ★ ⚠ same type
SCAMP2 p.Ala35Glu Uncertain significance ★ ⚠ same type
SCAMP2 p.Ala35Val Uncertain significance ★ ⚠ same type
SCAMP2 p.Ala46Val Uncertain significance ★ ⚠ same type
SCAMP2 p.Ala61Val Uncertain significance ★ ⚠ same type
SCAMP2 p.Ala97Gly 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/scamp2-p-pro196ser (accessed [today's date]).

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