Is CDKAL1 p.Arg162Ser (c.484C>A) pathogenic?

CDKAL1 p.Arg162Ser (c.484C>A) is classified Uncertain significance in CDKAL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-05). AlphaMissense: likely pathogenic (0.9805); Very rare (popmax 0.000255%, nfe).

How common is CDKAL1 p.Arg162Ser (c.484C>A) in the general population?

CDKAL1 p.Arg162Ser (c.484C>A) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about CDKAL1 p.Arg162Ser (c.484C>A)?

AlphaMissense predicts likely pathogenic (score 0.9805) — an in-silico prediction, not a clinical call.

CDKAL1 p.Arg162Ser

c.484C>A · rs866091749 · VCV2317184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9805 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9805	likely pathogenic
REVEL	0.477	indeterminate
SaProt	LLR -13.07	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 685 kb · p 0.00059 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,175,022 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000207% 3/1,451,774 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: CDKAL1
Protein: p.Arg162Ser
Coding: c.484C>A
MANE Select: NM_017774
dbSNP: rs866091749
Type: single nucleotide variant
Location: chr6:20758610 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 82.72
Residue 162: the mttase n-terminal domain

Full CDKAL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKAL1 p.Arg39Gln Likely benign ★★ ⚠ same type
CDKAL1 p.Ala126Val Uncertain significance ★ ⚠ same type
CDKAL1 p.Ala316Thr Uncertain significance ★ ⚠ same type
CDKAL1 p.Ala325Pro Uncertain significance ★ ⚠ same type
CDKAL1 p.Ala495Gly Uncertain significance ★ ⚠ same type
CDKAL1 p.Ala507Thr Uncertain significance ★ ⚠ same type
CDKAL1 p.Ala534Thr Uncertain significance ★ ⚠ same type
CDKAL1 p.Ala535Thr 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/cdkal1-p-arg162ser (accessed [today's date]).

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