Is CERK p.Ala7Val (c.20C>T) pathogenic?

CERK p.Ala7Val (c.20C>T) is classified Uncertain significance in CERK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: ambiguous (0.3861); Very rare (popmax 0.00801%, eas).

How common is CERK p.Ala7Val (c.20C>T) in the general population?

CERK p.Ala7Val (c.20C>T) is very rare (popmax 0.00801%, eas) (gnomAD).

What do computational predictors say about CERK p.Ala7Val (c.20C>T)?

AlphaMissense predicts ambiguous (score 0.3861) — an in-silico prediction, not a clinical call.

CERK p.Ala7Val

c.20C>T · VCV4001260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3861 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3861	ambiguous
REVEL	0.022	moderately benign-leaning
SaProt	LLR -7.02	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -0.91, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 51 kb · p 0.099 · regional, not allelic
Overall
CADD	21.0	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 0.00801% East Asian · 2/24,984 alleles

Filtering AF 0.00132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00111% 12/1,079,346 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00801%	12,492
South Asian	0.00241%	41,532
European (non-Finnish)	0.000918%	108,934

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.Ala7Val
Coding: c.20C>T
MANE Select: NM_022766
Type: single nucleotide variant
Location: chr22:46738129 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.86
Residue 7: 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.His113= Benign ★★ same type
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

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-ala7val (accessed [today's date]).

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