Is CSRNP1 p.Pro384Ser (c.1150C>T) pathogenic?

CSRNP1 p.Pro384Ser (c.1150C>T) is classified Uncertain significance in CSRNP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-31). AlphaMissense: likely benign (0.0791); Ultra-rare (popmax 0.0164%, mid).

How common is CSRNP1 p.Pro384Ser (c.1150C>T) in the general population?

CSRNP1 p.Pro384Ser (c.1150C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CSRNP1 p.Pro384Ser (c.1150C>T)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

CSRNP1 p.Pro384Ser

c.1150C>T · rs769413886 · VCV2373641

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.68, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 3,624 bp · p 0.0031 · regional, not allelic
Overall
CADD	11.66	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00186% 30/1,614,108 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Finnishnot grpmax-eligible	0.0109%	9,148
Remaining individualsnot grpmax-eligible	0.0032%	31,244
Admixed American	0.00167%	60,014
European (non-Finnish)	0.00153%	65,558
South Asian	0.0011%	91,088

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: CSRNP1
Protein: p.Pro384Ser
Coding: c.1150C>T
MANE Select: NM_033027
dbSNP: rs769413886
Type: single nucleotide variant
Location: chr3:39143675 (GRCh38)
Gene constraint: LOEUF 0.614 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 59.38
Residue 384: the 'disordered' region

Full CSRNP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSRNP1 p.Pro384Ala Uncertain significance ★ ⚠ same residue
CSRNP1 p.Pro55Thr Uncertain significance ★★ ⚠ same type
CSRNP1 p.Leu478Phe Likely benign ★★ same type
CSRNP1 p.Ala178Asp Uncertain significance ★ ⚠ same type
CSRNP1 p.Ala316Val Uncertain significance ★ ⚠ same type
CSRNP1 p.Ala392Thr Uncertain significance ★ ⚠ same type
CSRNP1 p.Ala564Pro Uncertain significance ★ ⚠ same type
CSRNP1 p.Ala564Thr 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/csrnp1-p-pro384ser (accessed [today's date]).

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