Is CERK p.His113= (c.339C>T) pathogenic?

CERK p.His113= (c.339C>T) is classified Benign in CERK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-21). Common (popmax 10.9%, afr) — too common for a highly-penetrant pathogenic allele.

CERK p.His113=

Q: How common is CERK p.His113= (c.339C>T) in the general population?

CERK p.His113= (c.339C>T) is common (popmax 10.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.339C>T · rs9627541 · VCV787511

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 10.9%, afr) — 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 -0.13	GERP -3.2, phastCons 0.087
Overall
CADD	2.552	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.9% African / African-American · 8,166/75,026 alleles

Filtering AF 10.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.6%

Overall 0.578% 9,324/1,614,060 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.9%	9
Remaining individualsnot grpmax-eligible	0.718%	139
Admixed American	0.665%	150
Middle Eastern	0.644%	155
Ashkenazi Jewishnot grpmax-eligible	0.0844%	1,184
South Asian	0.0231%	4,337
European (non-Finnish)	0.0191%	5,245

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: CERK
Protein: p.His113=
Coding: c.339C>T
MANE Select: NM_022766
dbSNP: rs9627541
Type: single nucleotide variant
Location: chr22:46720126 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.86
Residue 113: the 'required for binding to sulfatide and phosphoinositides' region; the 'essential for enzyme activity' region

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

Similar variants

CERK p.Pro509= Benign ★★ same type
CERK p.Thr461Met Benign ★★ same type
CERK p.Ala215Thr Uncertain significance ★ ⚠ same type
CERK p.Ala215Val Uncertain significance ★ ⚠ same type
CERK p.Ala238Ser Uncertain significance ★ ⚠ same type
CERK p.Ala238Thr Uncertain significance ★ ⚠ same type
CERK p.Ala254Thr Uncertain significance ★ ⚠ same type
CERK p.Ala258Val 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/cerk-p-his113 (accessed [today's date]).

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