Is CENPE p.Val62Met (c.184G>A) pathogenic?

CENPE p.Val62Met (c.184G>A) is classified Uncertain significance in CENPE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-23). AlphaMissense: ambiguous (0.4799); Very rare (popmax 0.00267%, afr).

How common is CENPE p.Val62Met (c.184G>A) in the general population?

CENPE p.Val62Met (c.184G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CENPE p.Val62Met (c.184G>A)?

AlphaMissense predicts ambiguous (score 0.4799) — an in-silico prediction, not a clinical call.

CENPE p.Val62Met

c.184G>A · rs1354503272 · VCV432293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4799 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.4799	ambiguous
REVEL	0.593	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 2,368 bp · p 1.4e-09 · regional, not allelic
Overall
CADD	27.2	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 0.00267% African / African-American · 2/74,864 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,506 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: CENPE
Protein: p.Val62Met
Coding: c.184G>A
MANE Select: NM_001813
dbSNP: rs1354503272
Type: single nucleotide variant
Location: chr4:103196217 (GRCh38)
Gene constraint: LOEUF 0.451 · pLI 1.00 (gnomAD)
Residue 62: the kinesin motor domain; an α-helix

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

Similar variants

CENPE p.Arg2279Cys Uncertain significance ★★ ⚠ same type
CENPE p.Arg760Ser Uncertain significance ★★ ⚠ same type
CENPE p.Asn1145Lys Uncertain significance ★★ ⚠ same type
CENPE p.Asn1165Ser Uncertain significance ★★ ⚠ same type
CENPE p.Asp1960Tyr Uncertain significance ★★ ⚠ same type
CENPE p.Asp954Asn Uncertain significance ★★ same type
CENPE p.Asp954Tyr Uncertain significance ★★ same type
CENPE p.Gln2022Glu 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/cenpe-p-val62met (accessed [today's date]).

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