Is CLUAP1 p.Arg141fs (c.420_427del) pathogenic?

CLUAP1 p.Arg141fs (c.420427del) is classified Uncertain significance in CLUAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-27). Very rare (popmax 0.00267%, afr).

How common is CLUAP1 p.Arg141fs (c.420_427del) in the general population?

CLUAP1 p.Arg141fs (c.420_427del) is very rare (popmax 0.00267%, afr) (gnomAD).

CLUAP1 p.Arg141fs

c.420_427del · rs2151049520 · VCV1476937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 5 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,038 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000137% 2/1,461,408 alleles · very rare

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: CLUAP1
Protein: p.Arg141fs
Coding: c.420_427del
MANE Select: NM_015041
dbSNP: rs2151049520
Type: Deletion
Location: chr16:3512396 (GRCh38)
Gene constraint: LOEUF 1.23 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.02

Full CLUAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLUAP1 c.14_22+16del Uncertain significance ★ same type
CLUAP1 p.Glu380_Asp382del Uncertain significance ★ same type
CLUAP1 p.Leu104_Tyr105insTer Uncertain significance ★ same type
CLUAP1 p.Met1fs Uncertain significance ★ same type
CLUAP1 c.134+16del Likely benign ★ same type
CLUAP1 c.22+13del Benign ★ same type
CLUAP1 c.579+12_579+13del Likely benign ★ same type
CLUAP1 c.579+13del Likely benign ★ 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/cluap1-p-arg141fs (accessed [today's date]).

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