Is SORT1 p.Ser111= (c.333A>G) pathogenic?

SORT1 p.Ser111= (c.333A>G) is classified Likely benign in SORT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-02). Ultra-rare (popmax 0.0384%, nfe).

How common is SORT1 p.Ser111= (c.333A>G) in the general population?

SORT1 p.Ser111= (c.333A>G) is ultra-rare (popmax 0.0384%, nfe) (gnomAD).

SORT1 p.Ser111=

c.333A>G · rs145159492 · VCV737274

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -4.2
Overall
CADD	6.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% European (non-Finnish) · 452/1,176,298 alleles

Filtering AF 0.0355% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0343%

Overall 0.0297% 478/1,609,922 alleles · ultra-rare exomes 441/1,457,754 · genomes 37/152,168 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0384%	2,602
Remaining individualsnot grpmax-eligible	0.0241%	4,157
African / African-American	0.00935%	10,691
Admixed American	0.00333%	29,994
Finnishnot grpmax-eligible	0.00312%	32,015

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.Ser111=
Coding: c.333A>G
MANE Select: NM_002959
dbSNP: rs145159492
Type: single nucleotide variant
Location: chr1:109369563 (GRCh38)
Gene constraint: LOEUF 0.553 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 83.27 · 17 PDB
Residue 111: the '10-bladed beta-propeller' region; a β-strand; the vps10p domain

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

Similar variants

SORT1 p.Asp358Tyr Benign ★★ ⚠ same type
SORT1 p.Ser746Asn Benign ★★ same type
SORT1 p.Ala340Thr Uncertain significance ★ ⚠ same type
SORT1 p.Arg288Lys Uncertain significance ★ ⚠ same type
SORT1 p.Arg311His Uncertain significance ★ ⚠ same type
SORT1 p.Arg326Ser Uncertain significance ★ ⚠ same type
SORT1 p.Arg382Gln Uncertain significance ★ ⚠ same type
SORT1 p.Arg392Leu 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/sort1-p-ser111 (accessed [today's date]).

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