Is SORT1 p.Ile763= (c.2289C>T) pathogenic?

SORT1 p.Ile763= (c.2289C>T) is classified Likely benign in SORT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-02-26). Ultra-rare (popmax 0.0494%, mid); Associated with SORT1-related disorder.

What condition is associated with SORT1 p.Ile763= (c.2289C>T)?

SORT1 p.Ile763= (c.2289C>T) is associated with SORT1-related disorder (ClinVar).

How common is SORT1 p.Ile763= (c.2289C>T) in the general population?

SORT1 p.Ile763= (c.2289C>T) is ultra-rare (popmax 0.0494%, mid) (gnomAD).

SORT1 p.Ile763=

c.2289C>T · rs369998819 · VCV3051097

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, mid)

Conditions

SORT1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.68	GERP -3.3
Overall
CADD	4.781	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0494% Middle Eastern · 3/6,072 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00717%

Overall 0.00137% 22/1,610,688 alleles · ultra-rare exomes 20/1,458,576 · genomes 2/152,112 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0494%	2,024
Remaining individualsnot grpmax-eligible	0.00321%	31,173
European (non-Finnish)	0.00136%	73,569
African / African-American	0.00134%	74,832

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: SORT1
Protein: p.Ile763=
Coding: c.2289C>T
MANE Select: NM_002959
dbSNP: rs369998819
Type: single nucleotide variant
Location: chr1:109314740 (GRCh38)
Gene constraint: LOEUF 0.553 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 83.27 · 17 PDB

Full SORT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SORT1-related disorder

Similar variants

SORT1 c.544-5A>G Likely benign same condition
SORT1 p.Phe198= Benign same condition
SORT1 p.Pro4= Benign same condition
SORT1 p.Pro747= Likely benign same condition
SORT1 p.Ser409= Likely benign same condition
SORT1 p.Ser540= Benign same condition
SORT1 p.Thr323= Benign same condition
SORT1 p.Asp358Tyr Benign ★★ ⚠ 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/sort1-p-ile763 (accessed [today's date]).

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