Is CSRNP1 p.Ser18Leu (c.53C>T) pathogenic?

CSRNP1 p.Ser18Leu (c.53C>T) is classified Likely benign in CSRNP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-09). AlphaMissense: likely benign (0.086); Very rare (popmax 0.00556%, amr).

How common is CSRNP1 p.Ser18Leu (c.53C>T) in the general population?

CSRNP1 p.Ser18Leu (c.53C>T) is very rare (popmax 0.00556%, amr) (gnomAD).

What do computational predictors say about CSRNP1 p.Ser18Leu (c.53C>T)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

CSRNP1 p.Ser18Leu

c.53C>T · rs759995863 · VCV3078366

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00556%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -9.99	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	GERP -0.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 3,624 bp · p 0.0031 · regional, not allelic
Overall
CADD	18.6	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 0.00556% Admixed American · 3/53,954 alleles

Filtering AF 0.00147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000709%

Overall 0.000774% 11/1,420,460 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00556%	17,985
South Asian	0.00117%	85,432
European (non-Finnish)	0.000604%	165,527

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.Ser18Leu
Coding: c.53C>T
MANE Select: NM_033027
dbSNP: rs759995863
Type: single nucleotide variant
Location: chr3:39146630 (GRCh38)
Gene constraint: LOEUF 0.614 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 59.38
Residue 18: the 'disordered' region

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

Similar variants

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
CSRNP1 p.Arg106His 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-ser18leu (accessed [today's date]).

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