Is CLUAP1 p.Asp362Asn (c.1084G>A) pathogenic?

CLUAP1 p.Asp362Asn (c.1084G>A) is classified Uncertain significance in CLUAP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.0867); Ultra-rare (popmax 0.0404%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with CLUAP1 p.Asp362Asn (c.1084G>A)?

CLUAP1 p.Asp362Asn (c.1084G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is CLUAP1 p.Asp362Asn (c.1084G>A) in the general population?

CLUAP1 p.Asp362Asn (c.1084G>A) is ultra-rare (popmax 0.0404%, nfe) (gnomAD).

What do computational predictors say about CLUAP1 p.Asp362Asn (c.1084G>A)?

AlphaMissense predicts likely benign (score 0.0867) — an in-silico prediction, not a clinical call.

CLUAP1 p.Asp362Asn

c.1084G>A · rs142451935 · VCV843767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0867 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0404%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0867	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -8.80	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 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 35 kb · p 0.32 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0404% European (non-Finnish) · 477/1,179,988 alleles

Filtering AF 0.0374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0362%

Overall 0.0327% 528/1,614,102 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0404%	2,474
Finnishnot grpmax-eligible	0.0328%	3,049
East Asian	0.0201%	4,987
Remaining individualsnot grpmax-eligible	0.0176%	5,683
African / African-American	0.00666%	15,007
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00333%	30,006
South Asian	0.0022%	45,538

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.Asp362Asn
Coding: c.1084G>A
MANE Select: NM_015041
dbSNP: rs142451935
Type: single nucleotide variant
Location: chr16:3532833 (GRCh38)
Gene constraint: LOEUF 1.23 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.02
Residue 362: the 'disordered' region

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLUAP1 p.Lys200Glu Uncertain significance ★★ ⚠ same condition
CLUAP1 c.496-9G>A Uncertain significance same condition
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-asp362asn (accessed [today's date]).

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