Is SPPL2A p.Ser69= (c.207C>T) pathogenic?

SPPL2A p.Ser69= (c.207C>T) is classified Likely benign in SPPL2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-12). No allele count reported in gnomAD v4.1 (AN 1,591,146).

How common is SPPL2A p.Ser69= (c.207C>T) in the general population?

SPPL2A p.Ser69= (c.207C>T) is no allele count reported in gnomAD v4.1 (AN 1,591,146) (gnomAD).

SPPL2A p.Ser69=

c.207C>T · VCV3625235

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,591,146)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.33	GERP -2.2, phastCons 0.007
Overall
CADD	7.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,591,146). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SPPL2A
Protein: p.Ser69=
Coding: c.207C>T
MANE Select: NM_032802
Type: single nucleotide variant
Location: chr15:50748841 (GRCh38)
Gene constraint: LOEUF 1.074 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 2 PDB
Residue 69: the pa domain

Full SPPL2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SPPL2A p.Ala179Val Uncertain significance ★★ ⚠ same type
SPPL2A p.Ala298Val Uncertain significance ★★ ⚠ same type
SPPL2A p.Ala480Thr Uncertain significance ★★ ⚠ same type
SPPL2A p.Arg281Cys Uncertain significance ★★ ⚠ same type
SPPL2A p.Arg281His Uncertain significance ★★ ⚠ same type
SPPL2A p.Arg424Thr Uncertain significance ★★ ⚠ same type
SPPL2A p.Arg483His Uncertain significance ★★ same type
SPPL2A p.Asn66Thr Uncertain significance ★★ ⚠ same type

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/sppl2a-p-ser69 (accessed [today's date]).

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