Is CENPU p.Ala115Val (c.344C>T) pathogenic?

CENPU p.Ala115Val (c.344C>T) is classified Uncertain significance in CENPU (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely benign (0.1194); Absent from gnomAD v4.1.

How common is CENPU p.Ala115Val (c.344C>T) in the general population?

CENPU p.Ala115Val (c.344C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CENPU p.Ala115Val (c.344C>T)?

AlphaMissense predicts likely benign (score 0.1194) — an in-silico prediction, not a clinical call.

CENPU p.Ala115Val

c.344C>T · VCV3265954

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1194 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1194	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -5.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.40	acceptor loss · deltas
Pangolin	Δ0.48	loss · gain 0.15 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.7	GERP -0.24, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 39 kb · p 0.37 · regional, not allelic
Overall
CADD	17.15	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

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: CENPU
Protein: p.Ala115Val
Coding: c.344C>T
MANE Select: NM_024629
Type: single nucleotide variant
Location: chr4:184717173 (GRCh38)
Gene constraint: LOEUF 1.207 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.09 · 18 PDB
Residue 115: the 'disordered' region

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

Similar variants

CENPU p.Ala169Thr Uncertain significance ★ ⚠ same type
CENPU p.Ala201Ser Uncertain significance ★ ⚠ same type
CENPU p.Ala400Thr Uncertain significance ★ ⚠ same type
CENPU p.Ala79Pro Uncertain significance ★ ⚠ same type
CENPU p.Arg161His Uncertain significance ★ ⚠ same type
CENPU p.Arg19Cys Uncertain significance ★ ⚠ same type
CENPU p.Arg347Thr Uncertain significance ★ ⚠ same type
CENPU p.Arg4Trp 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/cenpu-p-ala115val (accessed [today's date]).

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