Is CENPB p.Phe316Ser (c.947T>C) pathogenic?

CENPB p.Phe316Ser (c.947T>C) is classified Uncertain significance in CENPB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). AlphaMissense: likely pathogenic (0.6587); Ultra-rare (popmax 0.0181%, eas).

How common is CENPB p.Phe316Ser (c.947T>C) in the general population?

CENPB p.Phe316Ser (c.947T>C) is ultra-rare (popmax 0.0181%, eas) (gnomAD).

What do computational predictors say about CENPB p.Phe316Ser (c.947T>C)?

AlphaMissense predicts likely pathogenic (score 0.6587) — an in-silico prediction, not a clinical call.

CENPB p.Phe316Ser

c.947T>C · VCV3265863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6587 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0181%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6587	likely pathogenic
REVEL	0.332	indeterminate
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 1,400 bp · p 0.00023 · regional, not allelic
Overall
CADD	24.7	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 0.0181% East Asian · 8/44,100 alleles

Filtering AF 0.00897% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0065%

Overall 0.0005% 8/1,598,732 alleles · ultra-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: CENPB
Protein: p.Phe316Ser
Coding: c.947T>C
MANE Select: NM_001810
Type: single nucleotide variant
Location: chr20:3785537 (GRCh38)
Gene constraint: LOEUF 0.828 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.88 · 4 PDB

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

Similar variants

CENPB p.Phe316Val Uncertain significance ★ ⚠ same residue
CENPB p.Ala174Pro Uncertain significance ★ ⚠ same type
CENPB p.Ala231Thr Uncertain significance ★ ⚠ same type
CENPB p.Ala301Pro Uncertain significance ★ ⚠ same type
CENPB p.Ala345Thr Uncertain significance ★ ⚠ same type
CENPB p.Ala381Val Uncertain significance ★ ⚠ same type
CENPB p.Arg175Gln Uncertain significance ★ ⚠ same type
CENPB p.Arg219Cys 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/cenpb-p-phe316ser (accessed [today's date]).

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