Is CLUAP1 p.Ser2Phe (c.5C>T) pathogenic?

CLUAP1 p.Ser2Phe (c.5C>T) is classified Uncertain significance in CLUAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely pathogenic (0.9884); Very rare (popmax 0.000765%, nfe).

How common is CLUAP1 p.Ser2Phe (c.5C>T) in the general population?

CLUAP1 p.Ser2Phe (c.5C>T) is very rare (popmax 0.000765%, nfe) (gnomAD).

What do computational predictors say about CLUAP1 p.Ser2Phe (c.5C>T)?

AlphaMissense predicts likely pathogenic (score 0.9884) — an in-silico prediction, not a clinical call.

CLUAP1 p.Ser2Phe

c.5C>T · VCV3637795

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9884 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000765%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9884	likely pathogenic · top 3% in CLUAP1
REVEL	0.422	indeterminate
SaProt	LLR -15.54	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 7.3	GERP 2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 35 kb · p 0.32 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.000765% European (non-Finnish) · 9/1,176,968 alleles

Filtering AF 0.00036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000261%

Overall 0.000622% 9/1,447,222 alleles · very rare

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.Ser2Phe
Coding: c.5C>T
MANE Select: NM_015041
Type: single nucleotide variant
Location: chr16:3501072 (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.Ser2Cys 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-ser2phe (accessed [today's date]).

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