Is CENPE p.Val338= (c.1014A>G) pathogenic?

CENPE p.Val338= (c.1014A>G) is classified Benign in CENPE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-26). Common (popmax 20%, nfe) — too common for a highly-penetrant pathogenic allele.

CENPE p.Val338=

Q: How common is CENPE p.Val338= (c.1014A>G) in the general population?

CENPE p.Val338= (c.1014A>G) is common (popmax 20%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1014A>G · rs17217250 · VCV1252287

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 20%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.45	GERP -4.7, phastCons 0.18
Overall
CADD	7.793	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20% European (non-Finnish) · 229,543/1,148,890 alleles

Filtering AF 19.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.9%

Overall 18.8% 293,490/1,559,984 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	29.4%	3
Ashkenazi Jewishnot grpmax-eligible	21%	5
European (non-Finnish)grpmax	20%	5
Amishnot grpmax-eligible	18.5%	5
Remaining individualsnot grpmax-eligible	18.2%	6
Middle Eastern	17.4%	6
East Asian	16.5%	6
Admixed American	13.8%	7
South Asian	10.5%	10
African / African-American	5.6%	18

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val338=
Coding: c.1014A>G
MANE Select: NM_001813
dbSNP: rs17217250
Type: single nucleotide variant
Location: chr4:103181406 (GRCh38)
Gene constraint: LOEUF 0.451 · pLI 1.00 (gnomAD)

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-val338 (accessed [today's date]).

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