Is SP1 p.Ser319= (c.957C>G) pathogenic?

SP1 p.Ser319= (c.957C>G) is classified Likely benign in SP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-20). Absent from gnomAD v4.1.

How common is SP1 p.Ser319= (c.957C>G) in the general population?

SP1 p.Ser319= (c.957C>G) is absent from gnomAD v4.1 (gnomAD).

SP1 p.Ser319=

c.957C>G · rs1592554584 · VCV745328

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.62	phastCons 1
Overall
CADD	10.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SP1
Protein: p.Ser319=
Coding: c.957C>G
MANE Select: NM_138473
dbSNP: rs1592554584
Type: single nucleotide variant
Location: chr12:53382904 (GRCh38)
Gene constraint: LOEUF 0.169 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 39.98 · 11 PDB
Residue 319: the 'transactivation domain b (gln-rich)' region

Full SP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SP1 p.Leu529= Benign ★★ same type
SP1 p.Phe785= Likely benign ★★ same type
SP1 p.Ala13Gly Uncertain significance ★ ⚠ same type
SP1 p.Ala210Thr Uncertain significance ★ ⚠ same type
SP1 p.Ala227Gly Uncertain significance ★ ⚠ same type
SP1 p.Ala275Pro Uncertain significance ★ ⚠ same type
SP1 p.Ala429Val Uncertain significance ★ ⚠ same type
SP1 p.Ala513Thr 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/sp1-p-ser319 (accessed [today's date]).

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