Is CLUAP1 p.Glu323Asp (c.969A>C) pathogenic?

CLUAP1 p.Glu323Asp (c.969A>C) is classified Likely benign in CLUAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-03). AlphaMissense: likely benign (0.0725); Rare (popmax 0.168%, sas).

How common is CLUAP1 p.Glu323Asp (c.969A>C) in the general population?

CLUAP1 p.Glu323Asp (c.969A>C) is rare (popmax 0.168%, sas) (gnomAD).

What do computational predictors say about CLUAP1 p.Glu323Asp (c.969A>C)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

CLUAP1 p.Glu323Asp

c.969A>C · rs533805081 · VCV1116816

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.168%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -6.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.99	GERP -5.1
Regional constraint	o/e 1.04	unconstrained · MANE · 35 kb · p 0.32 · regional, not allelic
Overall
CADD	0.599	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 0.168% South Asian · 153/91,074 alleles

Filtering AF 0.146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.138%

Overall 0.0106% 171/1,614,028 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.168%	595
Remaining individualsnot grpmax-eligible	0.0176%	5,682
East Asian	0.00223%	44,866
European (non-Finnish)	0.000508%	196,666

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.Glu323Asp
Coding: c.969A>C
MANE Select: NM_015041
dbSNP: rs533805081
Type: single nucleotide variant
Location: chr16:3530608 (GRCh38)
Gene constraint: LOEUF 1.23 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.02
Residue 323: the 'disordered' region

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

Similar variants

CLUAP1 p.Glu323Lys 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
CLUAP1 p.Arg332Gln 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-glu323asp (accessed [today's date]).

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