Is SAE1 p.Pro323= (c.969T>C) pathogenic?

SAE1 p.Pro323= (c.969T>C) is classified Likely benign in SAE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-28). Absent from gnomAD v4.1.

How common is SAE1 p.Pro323= (c.969T>C) in the general population?

SAE1 p.Pro323= (c.969T>C) is absent from gnomAD v4.1 (gnomAD).

SAE1 p.Pro323=

c.969T>C · VCV3791766

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.
REVEL	0.1	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP 0.33, phastCons 0.37
Overall
CADD	9.047	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: SAE1
Protein: p.Pro323=
Coding: c.969T>C
MANE Select: NM_005500
Type: single nucleotide variant
Location: chr19:47209179 (GRCh38)
Gene constraint: LOEUF 0.49 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 91.78 · 14 PDB
Residue 323: an α-helix

Full SAE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SAE1 p.Tyr262= Benign ★★ same type
SAE1 p.Ala128Gly Uncertain significance ★ ⚠ same type
SAE1 p.Ala231Val Uncertain significance ★ ⚠ same type
SAE1 p.Arg235Cys Uncertain significance ★ ⚠ same type
SAE1 p.Arg35Trp Uncertain significance ★ ⚠ same type
SAE1 p.Arg38Gln Uncertain significance ★ ⚠ same type
SAE1 p.Arg83Cys Uncertain significance ★ ⚠ same type
SAE1 p.Arg89Gln 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/sae1-p-pro323 (accessed [today's date]).

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