Is SCFD1 p.Pro587Ser (c.1759C>T) pathogenic?

SCFD1 p.Pro587Ser (c.1759C>T) is classified Uncertain significance in SCFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). AlphaMissense: likely benign (0.2748); Absent from gnomAD v4.1.

How common is SCFD1 p.Pro587Ser (c.1759C>T) in the general population?

SCFD1 p.Pro587Ser (c.1759C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCFD1 p.Pro587Ser (c.1759C>T)?

AlphaMissense predicts likely benign (score 0.2748) — an in-silico prediction, not a clinical call.

SCFD1 p.Pro587Ser

c.1759C>T · rs2502522187 · VCV2620527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2748 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2748	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -9.33	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 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 113 kb · p 9.5e-06 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SCFD1
Protein: p.Pro587Ser
Coding: c.1759C>T
MANE Select: NM_016106
dbSNP: rs2502522187
Type: single nucleotide variant
Location: chr14:30721906 (GRCh38)
Gene constraint: LOEUF 0.809 · pLI 0.23 (gnomAD)
Structure: AlphaFold pLDDT 85.70

Full SCFD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCFD1 p.Ile70Thr Uncertain significance ★★ ⚠ same type
SCFD1 p.Ala134Val Uncertain significance ★ ⚠ same type
SCFD1 p.Ala206Asp Uncertain significance ★ ⚠ same type
SCFD1 p.Ala371Val Uncertain significance ★ ⚠ same type
SCFD1 p.Ala498Thr Uncertain significance ★ ⚠ same type
SCFD1 p.Ala503Thr Uncertain significance ★ ⚠ same type
SCFD1 p.Arg107Gln Uncertain significance ★ ⚠ same type
SCFD1 p.Arg357Gln 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/scfd1-p-pro587ser (accessed [today's date]).

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