Is SPEG p.Pro2845= (c.8535T>C) pathogenic?

SPEG p.Pro2845= (c.8535T>C) is classified Benign/Likely benign in SPEG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-16). Rare (popmax 0.66%, eas).

How common is SPEG p.Pro2845= (c.8535T>C) in the general population?

SPEG p.Pro2845= (c.8535T>C) is rare (popmax 0.66%, eas) (gnomAD).

SPEG p.Pro2845=

c.8535T>C · rs201822382 · VCV739320

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.66%, eas)

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.7	GERP -2.4
Overall
CADD	2.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.66% East Asian · 291/44,112 alleles

Filtering AF 0.597% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.573%

Overall 0.0206% 328/1,592,040 alleles · rare exomes 265/1,459,518 · genomes 63/132,522 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.66%	152
Remaining individualsnot grpmax-eligible	0.0516%	1,939
South Asian	0.00443%	22,566
Admixed American	0.00176%	56,956

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.Pro2845=
Coding: c.8535T>C
MANE Select: NM_005876
dbSNP: rs201822382
Type: single nucleotide variant
Location: chr2:219489553 (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-pro2845 (accessed [today's date]).

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