Is CLUAP1 p.Arg45Lys (c.134G>A) pathogenic?

CLUAP1 p.Arg45Lys (c.134G>A) is classified Uncertain significance in CLUAP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-01-17). AlphaMissense: likely pathogenic (0.649); Very rare (popmax 0.00545%, afr).

How common is CLUAP1 p.Arg45Lys (c.134G>A) in the general population?

CLUAP1 p.Arg45Lys (c.134G>A) is very rare (popmax 0.00545%, afr) (gnomAD).

What do computational predictors say about CLUAP1 p.Arg45Lys (c.134G>A)?

AlphaMissense predicts likely pathogenic (score 0.649) — an in-silico prediction, not a clinical call.

CLUAP1 p.Arg45Lys

c.134G>A · rs774939873 · VCV2790201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.649 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00545%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.649	likely pathogenic
REVEL	0.147	moderately benign-leaning
SaProt	LLR -10.16	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.93	donor loss · deltas
Pangolin	Δ0.82	loss · gain 0.20 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 35 kb · p 0.32 · regional, not allelic
Overall
CADD	33.0	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 0.00545% African / African-American · 4/73,398 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.000258% 4/1,549,764 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.Arg45Lys
Coding: c.134G>A
MANE Select: NM_015041
dbSNP: rs774939873
Type: single nucleotide variant
Location: chr16:3504831 (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 p.Ala152Glu Uncertain significance ★★ ⚠ same type
CLUAP1 p.Ala188Gly Uncertain significance ★★ ⚠ same type
CLUAP1 p.Ala339Thr Uncertain significance ★★ ⚠ same type
CLUAP1 p.Arg20Gln Uncertain significance ★★ same type
CLUAP1 p.Arg228Gln Uncertain significance ★★ ⚠ same type
CLUAP1 p.Arg304His Uncertain significance ★★ ⚠ same type
CLUAP1 p.Arg332Gln Uncertain significance ★★ ⚠ same type
CLUAP1 p.Asn296Lys 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/cluap1-p-arg45lys (accessed [today's date]).

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