Is CENPC p.Ser90Leu (c.269C>T) pathogenic?

CENPC p.Ser90Leu (c.269C>T) is classified Uncertain significance in CENPC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely benign (0.0893); Absent from gnomAD v4.1.

How common is CENPC p.Ser90Leu (c.269C>T) in the general population?

CENPC p.Ser90Leu (c.269C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CENPC p.Ser90Leu (c.269C>T)?

AlphaMissense predicts likely benign (score 0.0893) — an in-silico prediction, not a clinical call.

CENPC p.Ser90Leu

c.269C>T · rs774757917 · VCV2622633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0893 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,834)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0893	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -7.72	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 3	GERP 0.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 73 kb · p 0.0018 · regional, not allelic
Overall
CADD	21.5	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

No allele count reported in gnomAD v4.1 (AN 1,603,834). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CENPC
Protein: p.Ser90Leu
Coding: c.269C>T
MANE Select: NM_001812
dbSNP: rs774757917
Type: single nucleotide variant
Location: chr4:67530877 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.33 · 17 PDB
Residue 90: the 'disordered' region

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

Similar variants

CENPC p.Ala165Thr Uncertain significance ★ ⚠ same type
CENPC p.Ala23Val Uncertain significance ★ ⚠ same type
CENPC p.Ala313Val Uncertain significance ★ ⚠ same type
CENPC p.Ala324Thr Uncertain significance ★ ⚠ same type
CENPC p.Ala783Glu Uncertain significance ★ ⚠ same type
CENPC p.Ala783Thr Uncertain significance ★ ⚠ same type
CENPC p.Arg24His Uncertain significance ★ ⚠ same type
CENPC p.Arg272Gln 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/cenpc-p-ser90leu (accessed [today's date]).

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