Is SP9 p.Ser82Ter (c.245C>A) pathogenic?

SP9 p.Ser82Ter (c.245C>A) is classified Pathogenic in SP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-05). No allele count reported in gnomAD v4.1 (AN 1,497,580); Associated with neurodevelopmental disorder.

What condition is associated with SP9 p.Ser82Ter (c.245C>A)?

SP9 p.Ser82Ter (c.245C>A) is associated with neurodevelopmental disorder (ClinVar).

How common is SP9 p.Ser82Ter (c.245C>A) in the general population?

SP9 p.Ser82Ter (c.245C>A) is no allele count reported in gnomAD v4.1 (AN 1,497,580) (gnomAD).

SP9 p.Ser82Ter

c.245C>A · VCV4813568

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,497,580)

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.94, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,497,580). 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: SP9
Protein: p.Ser82Ter
Coding: c.245C>A
MANE Select: NM_001145250
Type: single nucleotide variant
Location: chr2:174336330 (GRCh38)
Gene constraint: LOEUF 0.731 · pLI 0.58 (gnomAD)
Structure: AlphaFold pLDDT 49.04

Full SP9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SP9 p.Ser82Leu Uncertain significance ★ ⚠ same residue
SP9 p.Ser112Ala Uncertain significance ★★ ⚠ same type
SP9 p.Ala462= Likely benign ★★ same type
SP9 p.Glu378Gly Pathogenic ★ same type
SP9 p.Ala176Val Uncertain significance ★ ⚠ same type
SP9 p.Ala241Ser Uncertain significance ★ ⚠ same type
SP9 p.Ala242Thr Uncertain significance ★ ⚠ same type
SP9 p.Ala393Ser 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/sp9-p-ser82ter (accessed [today's date]).

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