Is SCP2 p.Ser3Phe (c.8C>T) pathogenic?

SCP2 p.Ser3Phe (c.8C>T) is classified Uncertain significance in SCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-25). AlphaMissense: likely benign (0.0894); Very rare (popmax 8.53e-05%, nfe).

How common is SCP2 p.Ser3Phe (c.8C>T) in the general population?

SCP2 p.Ser3Phe (c.8C>T) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

What do computational predictors say about SCP2 p.Ser3Phe (c.8C>T)?

AlphaMissense predicts likely benign (score 0.0894) — an in-silico prediction, not a clinical call.

SCP2 p.Ser3Phe

c.8C>T · rs2150086298 · VCV1471293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0894 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0894	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -8.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -2.4
Regional constraint	o/e 0.90	unconstrained · MANE · 112 kb · p 0.012 · regional, not allelic
Overall
CADD	10.07	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 8.53e-05% European (non-Finnish) · 1/1,172,062 alleles

Overall 6.27e-05% 1/1,595,262 alleles · very rare exomes 1/1,442,904 · genomes 0/152,358 · joint denominator

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: SCP2
Protein: p.Ser3Phe
Coding: c.8C>T
MANE Select: NM_002979
dbSNP: rs2150086298
Type: single nucleotide variant
Location: chr1:52927404 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.39 · 2 PDB
Residue 3: a modified residue (phosphoserine)

Full SCP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCP2 c.825+1G>T Pathogenic/Likely pathogenic ★★ same type
SCP2 p.Gln371Ter Pathogenic ★★ same type
SCP2 p.Ala359Val Uncertain significance ★★ ⚠ same type
SCP2 p.Ala427Gly Uncertain significance ★★ ⚠ same type
SCP2 p.Ala46Val Uncertain significance ★★ ⚠ same type
SCP2 p.Ala545Asp Uncertain significance ★★ same type
SCP2 p.Arg105Cys Uncertain significance ★★ ⚠ same type
SCP2 p.Arg13Gln 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/scp2-p-ser3phe (accessed [today's date]).

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