Is SAE1 p.Phe296= (c.888C>T) pathogenic?

SAE1 p.Phe296= (c.888C>T) is classified Likely benign in SAE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Very rare (popmax 0.000424%, nfe).

How common is SAE1 p.Phe296= (c.888C>T) in the general population?

SAE1 p.Phe296= (c.888C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

SAE1 p.Phe296=

c.888C>T · VCV4836720

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.172	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP 3.7, phastCons 1
Overall
CADD	12.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,944 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,032 alleles · very rare exomes 5/1,461,790 · genomes 0/152,242 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SAE1
Protein: p.Phe296=
Coding: c.888C>T
MANE Select: NM_005500
Type: single nucleotide variant
Location: chr19:47203680 (GRCh38)
Gene constraint: LOEUF 0.49 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 91.78 · 14 PDB
Residue 296: a β-strand

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

Similar variants

SAE1 p.Phe296Cys Uncertain significance ★ same residue
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

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-phe296 (accessed [today's date]).

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