Is SPP2 p.Thr90= (c.270T>A) pathogenic?

SPP2 p.Thr90= (c.270T>A) is classified Benign in SPP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). Common (popmax 80%, sas) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with SPP2 p.Thr90= (c.270T>A)?

SPP2 p.Thr90= (c.270T>A) is associated with inherited retinal dystrophy (ClinVar).

SPP2 p.Thr90=

Q: How common is SPP2 p.Thr90= (c.270T>A) in the general population?

SPP2 p.Thr90= (c.270T>A) is common (popmax 80%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.270T>A · rs593668 · VCV1168002

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 80%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -9.9
Overall
CADD	0.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 80% South Asian · 72,811/91,020 alleles

Filtering AF 79.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 79.3%

Overall 71.8% 1,158,217/1,613,608 alleles · common exomes 1,053,174/1,461,544 · genomes 105,043/152,064 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	80%	1
Finnishnot grpmax-eligible	79.7%	1
Middle Eastern	75%	1
European (non-Finnish)	72.5%	1
Remaining individualsnot grpmax-eligible	72%	1
Amishnot grpmax-eligible	71.9%	1
Ashkenazi Jewishnot grpmax-eligible	68%	1
African / African-American	61.3%	2
Admixed American	60.5%	2
East Asian	58%	2

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: SPP2
Protein: p.Thr90=
Coding: c.270T>A
MANE Select: NM_006944
dbSNP: rs593668
Type: single nucleotide variant
Location: chr2:234058895 (GRCh38)
Gene constraint: LOEUF 1.655 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.68

Full SPP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPP2 p.Tyr197Ter Uncertain significance ★★ same condition
SPP2 c.*2G>A Benign/Likely benign ★★ same condition
SPP2 p.Asp36Glu Benign ★★ same condition
SPP2 p.Arg133His Conflicting classifications of pathogenicity ★ ⚠ same condition
SPP2 p.Arg62Gly Uncertain significance ★ same condition
SPP2 p.Arg93Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
SPP2 p.Cys92Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
SPP2 p.Gln128Ter Uncertain significance ★ same condition

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/spp2-p-thr90 (accessed [today's date]).

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