Is CRLF1 p.Pro2fs (c.4_10del) pathogenic?

CRLF1 p.Pro2fs (c.410del) is classified Likely pathogenic in CRLF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). Absent from gnomAD; Associated with cold-induced sweating syndrome.

What condition is associated with CRLF1 p.Pro2fs (c.4_10del)?

CRLF1 p.Pro2fs (c.4_10del) is associated with cold-induced sweating syndrome (ClinVar).

How common is CRLF1 p.Pro2fs (c.4_10del) in the general population?

CRLF1 p.Pro2fs (c.4_10del) is absent from gnomAD (gnomAD).

How is Cold-induced sweating syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CRLF1 p.Pro2fs

c.4_10del · rs2513397402 · VCV1705180

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cold-induced sweating syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -0.75, phastCons 1
Region caveats
Repeat context	tandem	(GCG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CRLF1
Protein: p.Pro2fs
Coding: c.4_10del
MANE Select: NM_004750
dbSNP: rs2513397402
Type: Deletion
Location: chr19:18606647 (GRCh38)
Gene constraint: LOEUF 1.045 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.15 · 1 PDB

Full CRLF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cold-induced sweating syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cold-induced sweating syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Childhood

Similar variants

CRLF1 p.Gln11fs Pathogenic ★★ same condition
CRLF1 p.Met1fs Likely pathogenic ★ same condition
CRLF1 p.Pro2= Likely benign ★ same residue
CRLF1 p.Pro239fs Pathogenic ★★ same condition
CRLF1 p.Met1Val Likely pathogenic ★ same condition
CRLF1 p.Pro238fs Pathogenic ★★ same type
CRLF1 p.Ala202fs Likely pathogenic ★ same type
CRLF1 p.Arg275_Tyr276insTer Likely pathogenic ★ 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/crlf1-p-pro2fs (accessed [today's date]).

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