Is SAG p.Ser330Pro (c.988T>C) pathogenic?

SAG p.Ser330Pro (c.988T>C) is classified Uncertain significance in SAG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-22). AlphaMissense: likely pathogenic (0.9806); Absent from gnomAD v4.1.

How common is SAG p.Ser330Pro (c.988T>C) in the general population?

SAG p.Ser330Pro (c.988T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SAG p.Ser330Pro (c.988T>C)?

AlphaMissense predicts likely pathogenic (score 0.9806) — an in-silico prediction, not a clinical call.

SAG p.Ser330Pro

c.988T>C · rs2469819668 · VCV2831082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9806 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9806	likely pathogenic
REVEL	0.355	indeterminate
SaProt	LLR -16.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.8, phastCons 1
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: SAG
Protein: p.Ser330Pro
Coding: c.988T>C
MANE Select: NM_000541
dbSNP: rs2469819668
Type: single nucleotide variant
Location: chr2:233338719 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 7 PDB

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

Similar variants

SAG c.1023-2A>G Likely pathogenic ★★ same type
SAG c.1103-2A>C Pathogenic/Likely pathogenic ★★ same type
SAG c.136+2T>C Likely pathogenic ★★ same type
SAG c.136+2T>G Pathogenic/Likely pathogenic ★★ same type
SAG c.181+1G>A Likely pathogenic ★★ same type
SAG c.182-2A>G Pathogenic/Likely pathogenic ★★ same type
SAG c.376-2A>G Pathogenic/Likely pathogenic ★★ same type
SAG c.435+1G>A Likely pathogenic ★★ 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/sag-p-ser330pro (accessed [today's date]).

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