Is SCAMP2 p.Pro69Arg (c.206C>G) pathogenic?

SCAMP2 p.Pro69Arg (c.206C>G) is classified Uncertain significance in SCAMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). AlphaMissense: likely benign (0.128); Ultra-rare (popmax 0.0208%, nfe).

How common is SCAMP2 p.Pro69Arg (c.206C>G) in the general population?

SCAMP2 p.Pro69Arg (c.206C>G) is ultra-rare (popmax 0.0208%, nfe) (gnomAD).

What do computational predictors say about SCAMP2 p.Pro69Arg (c.206C>G)?

AlphaMissense predicts likely benign (score 0.128) — an in-silico prediction, not a clinical call.

SCAMP2 p.Pro69Arg

c.206C>G · VCV3316358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.128 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.128	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -9.04	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 28 kb · p 0.0057 · regional, not allelic
Overall
CADD	27.8	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 0.0208% European (non-Finnish) · 245/1,179,966 alleles

Filtering AF 0.0186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.0157% 253/1,614,108 alleles · ultra-rare exomes 241/1,461,746 · genomes 12/152,362 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0208%	4,816
Remaining individualsnot grpmax-eligible	0.008%	12,500
African / African-American	0.00266%	37,529
Admixed American	0.00167%	60,030

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: SCAMP2
Protein: p.Pro69Arg
Coding: c.206C>G
MANE Select: NM_005697
Type: single nucleotide variant
Location: chr15:74854040 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.30
Residue 69: the 'disordered' region

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-pro69arg (accessed [today's date]).

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