Is CLUAP1 p.Ala173Pro (c.517G>C) pathogenic?

CLUAP1 p.Ala173Pro (c.517G>C) is classified Uncertain significance in CLUAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-13). AlphaMissense: likely pathogenic (0.9638); Absent from gnomAD v4.1.

How common is CLUAP1 p.Ala173Pro (c.517G>C) in the general population?

CLUAP1 p.Ala173Pro (c.517G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLUAP1 p.Ala173Pro (c.517G>C)?

AlphaMissense predicts likely pathogenic (score 0.9638) — an in-silico prediction, not a clinical call.

CLUAP1 p.Ala173Pro

c.517G>C · rs757602852 · VCV2110768

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9638 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9638	likely pathogenic · top 7% in CLUAP1
REVEL	0.351	indeterminate
SaProt	LLR -12.82	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 35 kb · p 0.32 · regional, not allelic
Overall
CADD	29.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLUAP1
Protein: p.Ala173Pro
Coding: c.517G>C
MANE Select: NM_015041
dbSNP: rs757602852
Type: single nucleotide variant
Location: chr16:3515529 (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-ala173pro (accessed [today's date]).

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