Is CHUK p.Ser486= (c.1458C>T) pathogenic?

CHUK p.Ser486= (c.1458C>T) is classified Benign in CHUK (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 12.4%, mid) — too common for a highly-penetrant pathogenic allele.

CHUK p.Ser486=

Q: How common is CHUK p.Ser486= (c.1458C>T) in the general population?

CHUK p.Ser486= (c.1458C>T) is common (popmax 12.4%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1458C>T · rs17880383 · VCV1261345

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 12.4%, mid) — 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 5.2	GERP 1, phastCons 1
Overall
CADD	8.649	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.4% Middle Eastern · 751/6,050 alleles

Filtering AF 11.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.4%

Overall 5.13% 82,686/1,612,768 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	12.4%	8
Ashkenazi Jewishnot grpmax-eligible	9%	11
European (non-Finnish)	5.98%	17
Remaining individualsnot grpmax-eligible	5.18%	19
Admixed American	4.38%	23
Amishnot grpmax-eligible	3.4%	29
South Asian	1.48%	67
Finnishnot grpmax-eligible	1.15%	87
African / African-American	1.1%	91
East Asian	0.0268%	3,736

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: CHUK
Protein: p.Ser486=
Coding: c.1458C>T
MANE Select: NM_001278
dbSNP: rs17880383
Type: single nucleotide variant
Location: chr10:100204555 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.39 (gnomAD)
Structure: AlphaFold pLDDT 84.41 · 5 PDB

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

Similar variants

CHUK p.Ser486Ile Uncertain significance ★ ⚠ same residue
CHUK p.Arg365Gln Uncertain significance ★★ ⚠ same type
CHUK p.Arg424Cys Uncertain significance ★★ ⚠ same type
CHUK p.Arg563Cys Uncertain significance ★★ ⚠ same type
CHUK p.Arg563His Uncertain significance ★★ ⚠ same type
CHUK p.Gln226Pro Uncertain significance ★★ ⚠ same type
CHUK p.Gly346Arg Uncertain significance ★★ ⚠ same type
CHUK p.His520Arg 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/chuk-p-ser486 (accessed [today's date]).

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