Is SAG p.Pro44Ala (c.130C>G) pathogenic?

SAG p.Pro44Ala (c.130C>G) is classified Uncertain significance in SAG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.0697); Absent from gnomAD v4.1.

How common is SAG p.Pro44Ala (c.130C>G) in the general population?

SAG p.Pro44Ala (c.130C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SAG p.Pro44Ala (c.130C>G)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

SAG p.Pro44Ala

c.130C>G · VCV3616960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -8.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.94, phastCons 1
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Pro44Ala
Coding: c.130C>G
MANE Select: NM_000541
Type: single nucleotide variant
Location: chr2:233316129 (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-pro44ala (accessed [today's date]).

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