Is CLUAP1 p.Arg401Trp (c.1201C>T) pathogenic?

CLUAP1 p.Arg401Trp (c.1201C>T) is classified Benign in CLUAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1099); Common (popmax 27.3%, sas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CLUAP1 p.Arg401Trp (c.1201C>T)?

AlphaMissense predicts likely benign (score 0.1099) — an in-silico prediction, not a clinical call.

CLUAP1 p.Arg401Trp

Q: How common is CLUAP1 p.Arg401Trp (c.1201C>T) in the general population?

CLUAP1 p.Arg401Trp (c.1201C>T) is common (popmax 27.3%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1201C>T · rs9790 · VCV1170237

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1099 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 27.3%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1099	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -10.67	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 1.7, phastCons 0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 35 kb · p 0.32 · regional, not allelic
Overall
CADD	21.9	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 27.3% South Asian · 24,816/91,042 alleles

Filtering AF 27% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.9%

Overall 19.5% 313,978/1,613,740 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	27.3%	4
Admixed American	26.2%	4
European (non-Finnish)	19.8%	5
Remaining individualsnot grpmax-eligible	18.7%	5
Finnishnot grpmax-eligible	18.5%	5
Ashkenazi Jewishnot grpmax-eligible	17.8%	6
Middle Eastern	16.6%	6
Amishnot grpmax-eligible	14.5%	7
East Asian	13.8%	7
African / African-American	4.62%	22

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.Arg401Trp
Coding: c.1201C>T
MANE Select: NM_015041
dbSNP: rs9790
Type: single nucleotide variant
Location: chr16:3536230 (GRCh38)
Gene constraint: LOEUF 1.23 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.02
Residue 401: the 'disordered' region; a UniProt-annotated variant site (in)

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

Similar variants

CLUAP1 p.Arg401Gln Uncertain significance ★ ⚠ same residue
CLUAP1 p.Arg401Gly Uncertain significance ★ ⚠ same residue
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

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-arg401trp (accessed [today's date]).

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