Is CENPT p.Ser230Phe (c.689C>T) pathogenic?

CENPT p.Ser230Phe (c.689C>T) is classified Uncertain significance in CENPT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-27). AlphaMissense: likely benign (0.247); Very rare (popmax 0.00144%, nfe).

How common is CENPT p.Ser230Phe (c.689C>T) in the general population?

CENPT p.Ser230Phe (c.689C>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about CENPT p.Ser230Phe (c.689C>T)?

AlphaMissense predicts likely benign (score 0.247) — an in-silico prediction, not a clinical call.

CENPT p.Ser230Phe

c.689C>T · VCV3831598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.247 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.247	likely benign
REVEL	0.237	benign-leaning
SaProt	LLR -10.04	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.83, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 5,589 bp · p 0.92 · regional, not allelic
Overall
CADD	22.8	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 0.00144% European (non-Finnish) · 17/1,180,014 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00105% 17/1,613,952 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: CENPT
Protein: p.Ser230Phe
Coding: c.689C>T
MANE Select: NM_025082
Type: single nucleotide variant
Location: chr16:67831230 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.20 · 9 PDB
Residue 230: the 'flexible stalk domain' region

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

Similar variants

THAP11 p.Val230= Likely benign ★ same residue
THAP11 p.Ala100Ser Uncertain significance ★★ ⚠ same type
THAP11 p.Asn13Ser Uncertain significance ★★ ⚠ same type
THAP11 p.Asn86Ser Uncertain significance ★★ ⚠ same type
THAP11 p.Gln104Arg Uncertain significance ★★ ⚠ same type
THAP11 p.Gln168Glu Uncertain significance ★★ ⚠ same type
THAP11 p.Pro170Gln Uncertain significance ★★ ⚠ same type
THAP11 p.Thr139Ala 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/cenpt-p-ser230phe (accessed [today's date]).

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