Is SQOR p.Pro123Arg (c.368C>G) pathogenic?

SQOR p.Pro123Arg (c.368C>G) is classified Uncertain significance in SQOR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely pathogenic (0.826); Ultra-rare (popmax 0.0312%, eas).

How common is SQOR p.Pro123Arg (c.368C>G) in the general population?

SQOR p.Pro123Arg (c.368C>G) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about SQOR p.Pro123Arg (c.368C>G)?

AlphaMissense predicts likely pathogenic (score 0.826) — an in-silico prediction, not a clinical call.

SQOR p.Pro123Arg

c.368C>G · VCV3322553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.826 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.826	likely pathogenic
REVEL	0.567	indeterminate
SaProt	LLR -17.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.96 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.0312% East Asian · 14/44,894 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.000991% 16/1,614,018 alleles · ultra-rare exomes 14/1,461,866 · genomes 2/152,152 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,207
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	8.47e-05%	1,180,022

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: SQOR
Protein: p.Pro123Arg
Coding: c.368C>G
MANE Select: NM_021199
Type: single nucleotide variant
Location: chr15:45662088 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.42 · 8 PDB
Residue 123: an α-helix

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

Similar variants

SQOR p.Pro123Ser Uncertain significance ★ ⚠ same residue
SQOR p.Arg61His Uncertain significance ★★ ⚠ same type
SQOR p.Ala144Thr Uncertain significance ★ ⚠ same type
SQOR p.Ala162Thr Uncertain significance ★ ⚠ same type
SQOR p.Ala17Asp Uncertain significance ★ ⚠ same type
SQOR p.Ala346Val Uncertain significance ★ ⚠ same type
SQOR p.Ala39Val Uncertain significance ★ ⚠ same type
SQOR p.Ala72Val 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/sqor-p-pro123arg (accessed [today's date]).

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