Is CENPL p.Pro79Ser (c.235C>T) pathogenic?

CENPL p.Pro79Ser (c.235C>T) is classified Uncertain significance in CENPL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: likely pathogenic (0.728); Very rare (popmax 0.00188%, nfe).

How common is CENPL p.Pro79Ser (c.235C>T) in the general population?

CENPL p.Pro79Ser (c.235C>T) is very rare (popmax 0.00188%, nfe) (gnomAD).

What do computational predictors say about CENPL p.Pro79Ser (c.235C>T)?

AlphaMissense predicts likely pathogenic (score 0.728) — an in-silico prediction, not a clinical call.

CENPL p.Pro79Ser

c.235C>T · VCV3490383

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.728 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00188%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.728	likely pathogenic
REVEL	0.767	pathogenic-leaning
SaProt	LLR -9.89	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.099 · regional, not allelic
Overall
CADD	26.0	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 0.00188% European (non-Finnish) · 22/1,169,964 alleles

Filtering AF 0.00123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00144% 23/1,599,940 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00188%	53,180
Remaining individualsnot grpmax-eligible	0.00162%	61,738

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: CENPL
Protein: p.Pro79Ser
Coding: c.235C>T
MANE Select: NM_001387287
Type: single nucleotide variant
Location: chr1:173807452 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 83.44 · 12 PDB

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

Similar variants

CENPL p.Ala108Val Uncertain significance ★ ⚠ same type
CENPL p.Ala212Gly Uncertain significance ★ ⚠ same type
CENPL p.Ala227Thr Uncertain significance ★ ⚠ same type
CENPL p.Ala255Thr Uncertain significance ★ ⚠ same type
CENPL p.Arg16Ile Uncertain significance ★ ⚠ same type
CENPL p.Arg30Gln Uncertain significance ★ ⚠ same type
CENPL p.Arg30Pro Uncertain significance ★ ⚠ same type
CENPL p.Asn187Lys 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/cenpl-p-pro79ser (accessed [today's date]).

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