Is SNX2 p.Pro7Arg (c.20C>G) pathogenic?

SNX2 p.Pro7Arg (c.20C>G) is classified Uncertain significance in SNX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: ambiguous (0.3424); Very rare (popmax 0.000598%, nfe).

How common is SNX2 p.Pro7Arg (c.20C>G) in the general population?

SNX2 p.Pro7Arg (c.20C>G) is very rare (popmax 0.000598%, nfe) (gnomAD).

What do computational predictors say about SNX2 p.Pro7Arg (c.20C>G)?

AlphaMissense predicts ambiguous (score 0.3424) — an in-silico prediction, not a clinical call.

SNX2 p.Pro7Arg

c.20C>G · rs957416964 · VCV3167218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3424 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000598%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3424	ambiguous
REVEL	0.637	indeterminate
SaProt	LLR -7.33	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 27 kb · p 0.028 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000598% European (non-Finnish) · 7/1,171,414 alleles

Filtering AF 0.000249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00016%

Overall 0.00044% 7/1,592,484 alleles · very rare exomes 7/1,440,170 · genomes 0/152,314 · 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: SNX2
Protein: p.Pro7Arg
Coding: c.20C>G
MANE Select: NM_003100
dbSNP: rs957416964
Type: single nucleotide variant
Location: chr5:122775123 (GRCh38)
Gene constraint: LOEUF 0.521 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 76.87
Residue 7: the 'disordered' region

Full SNX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SNX2 c.226+2T>C Uncertain significance ★ same type
SNX2 c.227-1G>A Uncertain significance ★ same type
SNX2 c.644-2A>G Uncertain significance ★ same type
SNX2 p.Ala135Pro Uncertain significance ★ ⚠ same type
SNX2 p.Ala2Val Uncertain significance ★ ⚠ same type
SNX2 p.Ala519Asp Uncertain significance ★ ⚠ same type
SNX2 p.Arg398His Uncertain significance ★ same type
SNX2 p.Arg472Ter 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/snx2-p-pro7arg (accessed [today's date]).

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