Is SPEG p.Pro3160= (c.9480G>A) pathogenic?

SPEG p.Pro3160= (c.9480G>A) is classified Benign/Likely benign in SPEG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-19). Rare (popmax 0.234%, sas).

How common is SPEG p.Pro3160= (c.9480G>A) in the general population?

SPEG p.Pro3160= (c.9480G>A) is rare (popmax 0.234%, sas) (gnomAD).

SPEG p.Pro3160=

c.9480G>A · rs529902389 · VCV1588937

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.234%, sas)

⚠ 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.
REVEL	0.067	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -6.5	GERP -2.6
Overall
CADD	1.229	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.234% South Asian · 213/91,028 alleles

Filtering AF 0.208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.198%

Overall 0.0154% 249/1,613,166 alleles · rare exomes 241/1,460,910 · genomes 8/152,256 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.234%	427
Middle Eastern	0.033%	3,026
Remaining individualsnot grpmax-eligible	0.0224%	4,462
Admixed American	0.00334%	29,984
East Asian	0.00223%	44,838
Finnishnot grpmax-eligible	0.00157%	63,762
European (non-Finnish)	0.00136%	73,722

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.Pro3160=
Coding: c.9480G>A
MANE Select: NM_005876
dbSNP: rs529902389
Type: single nucleotide variant
Location: chr2:219492129 (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-pro3160 (accessed [today's date]).

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