Is RNPC3 p.Ser19del (c.48CTC[2]) pathogenic?

RNPC3 p.Ser19del (c.48CTC[2]) is classified Uncertain significance in RNPC3 (ClinVar, Single submitter, 1 submitter). Ultra-rare (popmax 0.0405%, sas); Associated with isolated growth hormone deficiency, type 5.

What condition is associated with RNPC3 p.Ser19del (c.48CTC[2])?

RNPC3 p.Ser19del (c.48CTC[2]) is associated with isolated growth hormone deficiency, type 5 (ClinVar).

How common is RNPC3 p.Ser19del (c.48CTC[2]) in the general population?

RNPC3 p.Ser19del (c.48CTC[2]) is ultra-rare (popmax 0.0405%, sas) (gnomAD).

How is Non-acquired isolated growth hormone deficiency inherited?

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

RNPC3 p.Ser19del

c.48CTC[2] · VCV3377745

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0405%, sas)

Conditions

isolated growth hormone deficiency, type 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP 0.91, phastCons 0.74
Overall
CADD	16.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0405% South Asian · 34/83,992 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00393% 61/1,550,916 alleles · ultra-rare exomes 56/1,398,614 · genomes 5/152,302 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0405%	2,470
European (non-Finnish)	0.00218%	45,861
Remaining individualsnot grpmax-eligible	0.00166%	60,076
African / African-American	0.00137%	73,178

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: RNPC3
Protein: p.Ser19del
Coding: c.48CTC[2]
MANE Select: NM_017619
Type: Microsatellite
Location: chr1:103526118 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.73 · 2 PDB
Residue 19: the 'necessary for interaction with pdcd7' region; the 'disordered' region

Full RNPC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

isolated growth hormone deficiency, type 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-acquired isolated growth hormone deficiency (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

RNPC3 c.894-2A>G Likely pathogenic ★★ same condition
RNPC3 p.Asn342His Uncertain significance ★★ ⚠ same condition
RNPC3 c.359+16A>G Benign ★★ same condition
RNPC3 p.Gly114= Benign ★★ same condition
RNPC3 p.Arg205Ter Pathogenic ★ same condition
RNPC3 p.Asn347fs Likely pathogenic ★ same condition
RNPC3 p.Asn342Thr Uncertain significance ★ ⚠ same condition
RNPC3 p.Asp287Asn Uncertain significance ★ ⚠ same condition

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/rnpc3-p-ser19del (accessed [today's date]).

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