Is CSRNP3 p.Ser20Pro (c.58T>C) pathogenic?

CSRNP3 p.Ser20Pro (c.58T>C) is classified Uncertain significance in CSRNP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-28). AlphaMissense: likely benign (0.324); Very rare (popmax 8.48e-05%, nfe).

How common is CSRNP3 p.Ser20Pro (c.58T>C) in the general population?

CSRNP3 p.Ser20Pro (c.58T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CSRNP3 p.Ser20Pro (c.58T>C)?

AlphaMissense predicts likely benign (score 0.324) — an in-silico prediction, not a clinical call.

CSRNP3 p.Ser20Pro

c.58T>C · rs1208527019 · VCV2607009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.324 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.324	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 63 kb · p 1.7e-06 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 8.48e-05% European (non-Finnish) · 1/1,179,894 alleles

Overall 6.2e-05% 1/1,614,040 alleles · very rare exomes 1/1,461,720 · genomes 0/152,320 · 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: CSRNP3
Protein: p.Ser20Pro
Coding: c.58T>C
MANE Select: NM_001172173
dbSNP: rs1208527019
Type: single nucleotide variant
Location: chr2:165595123 (GRCh38)
Gene constraint: LOEUF 0.387 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.42
Residue 20: the 'disordered' region

Full CSRNP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSRNP3 p.Ala188Asp Uncertain significance ★ ⚠ same type
CSRNP3 p.Ala230Thr Uncertain significance ★ ⚠ same type
CSRNP3 p.Ala306Thr Uncertain significance ★ ⚠ same type
CSRNP3 p.Ala314Val Uncertain significance ★ ⚠ same type
CSRNP3 p.Ala326Ser Uncertain significance ★ ⚠ same type
CSRNP3 p.Ala333Ser Uncertain significance ★ ⚠ same type
CSRNP3 p.Ala417Thr Uncertain significance ★ ⚠ same type
CSRNP3 p.Ala426Pro 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/csrnp3-p-ser20pro (accessed [today's date]).

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