Is CLUAP1 p.Ala15Val (c.44C>T) pathogenic?

CLUAP1 p.Ala15Val (c.44C>T) is classified Uncertain significance in CLUAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: ambiguous (0.4859); Very rare (popmax 0.00401%, afr).

How common is CLUAP1 p.Ala15Val (c.44C>T) in the general population?

CLUAP1 p.Ala15Val (c.44C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about CLUAP1 p.Ala15Val (c.44C>T)?

AlphaMissense predicts ambiguous (score 0.4859) — an in-silico prediction, not a clinical call.

CLUAP1 p.Ala15Val

c.44C>T · VCV3494023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4859	ambiguous
REVEL	0.226	benign-leaning
SaProt	LLR -9.37	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 35 kb · p 0.32 · regional, not allelic
Overall
CADD	26.2	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 0.00401% African / African-American · 3/74,882 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000275% 4/1,456,230 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,961
European (non-Finnish)	8.51e-05%	1,174,818

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.Ala15Val
Coding: c.44C>T
MANE Select: NM_015041
Type: single nucleotide variant
Location: chr16:3504741 (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.Ala15Thr 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-ala15val (accessed [today's date]).

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