Is CEND1 p.Pro28Leu (c.83C>T) pathogenic?

CEND1 p.Pro28Leu (c.83C>T) is classified Uncertain significance in CEND1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: likely benign (0.0696); Very rare (popmax 0.0021%, amr).

How common is CEND1 p.Pro28Leu (c.83C>T) in the general population?

CEND1 p.Pro28Leu (c.83C>T) is very rare (popmax 0.0021%, amr) (gnomAD).

What do computational predictors say about CEND1 p.Pro28Leu (c.83C>T)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

CEND1 p.Pro28Leu

c.83C>T · rs778768643 · VCV2208327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0021%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -8.11	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 1.9	GERP -1.9, phastCons 0.009
Regional constraint	o/e 1.06	unconstrained · MANE · 446 bp · p 0.41 · regional, not allelic
Overall
CADD	13.25	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

Grpmax group 0.0021% Admixed American · 1/47,708 alleles

Filtering AF 0.000635% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00049%

Overall 0.00111% 17/1,536,630 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0021%	47,708
Remaining individualsnot grpmax-eligible	0.0017%	58,912
African / African-American	0.00139%	72,120
South Asian	0.00123%	81,286
European (non-Finnish)	0.00114%	87,826

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: CEND1
Protein: p.Pro28Leu
Coding: c.83C>T
MANE Select: NM_016564
dbSNP: rs778768643
Type: single nucleotide variant
Location: chr11:788494 (GRCh38)
Gene constraint: LOEUF 1.187 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 60.87
Residue 28: the 'disordered' region

Full CEND1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEND1 p.Ala101Gly Uncertain significance ★ ⚠ same type
CEND1 p.Ala101Thr Uncertain significance ★ ⚠ same type
CEND1 p.Ala101Val Uncertain significance ★ ⚠ same type
CEND1 p.Ala106Ser Uncertain significance ★ ⚠ same type
CEND1 p.Ala54Asp Uncertain significance ★ ⚠ same type
CEND1 p.Ala54Ser Uncertain significance ★ ⚠ same type
CEND1 p.Ala70Pro Uncertain significance ★ ⚠ same type
CEND1 p.Ala81Val 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/cend1-p-pro28leu (accessed [today's date]).

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