Is SPP2 p.Tyr35= (c.105C>T) pathogenic?

SPP2 p.Tyr35= (c.105C>T) is classified Likely benign in SPP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). Very rare (popmax 0.00267%, afr); Associated with inherited retinal dystrophy.

What condition is associated with SPP2 p.Tyr35= (c.105C>T)?

SPP2 p.Tyr35= (c.105C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is SPP2 p.Tyr35= (c.105C>T) in the general population?

SPP2 p.Tyr35= (c.105C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

SPP2 p.Tyr35=

c.105C>T · rs753888543 · VCV3027530

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.5	GERP -6
Overall
CADD	0.211	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,914 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00143% 23/1,613,914 alleles · very rare exomes 20/1,461,738 · genomes 3/152,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,457
East Asian	0.00223%	44,886
European (non-Finnish)	0.00161%	62,103
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Tyr35=
Coding: c.105C>T
MANE Select: NM_006944
dbSNP: rs753888543
Type: single nucleotide variant
Location: chr2:234050990 (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.Thr90= 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

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-tyr35 (accessed [today's date]).

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