Is SPEG p.Arg2007Pro (c.6020G>C) pathogenic?

SPEG p.Arg2007Pro (c.6020G>C) is classified Uncertain significance in SPEG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-20). AlphaMissense: likely benign (0.2202); Very rare (popmax 0.0026%, nfe).

How common is SPEG p.Arg2007Pro (c.6020G>C) in the general population?

SPEG p.Arg2007Pro (c.6020G>C) is very rare (popmax 0.0026%, nfe) (gnomAD).

What do computational predictors say about SPEG p.Arg2007Pro (c.6020G>C)?

AlphaMissense predicts likely benign (score 0.2202) — an in-silico prediction, not a clinical call.

SPEG p.Arg2007Pro

c.6020G>C · rs747077634 · VCV1348293

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2202 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0026%, nfe)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2202	likely benign
REVEL	0.3	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Regional constraint	o/e 1.05	unconstrained · MANE · 7,108 bp · p 0.064 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0026% European (non-Finnish) · 29/1,114,358 alleles

Filtering AF 0.00183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00158%

Overall 0.00275% 40/1,453,886 alleles · very rare exomes 38/1,301,836 · genomes 2/152,050 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0118%	8,484
Remaining individualsnot grpmax-eligible	0.0107%	9,320
European (non-Finnish)grpmax	0.0026%	38,426

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SPEG
Protein: p.Arg2007Pro
Coding: c.6020G>C
MANE Select: NM_005876
dbSNP: rs747077634
Type: single nucleotide variant
Location: chr2:219483483 (GRCh38)

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

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/speg-p-arg2007pro (accessed [today's date]).

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