Is CKAP2 p.Ser153Gly (c.457A>G) pathogenic?

CKAP2 p.Ser153Gly (c.457A>G) is classified Likely benign in CKAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0636); Very rare (popmax 0.00932%, nfe).

How common is CKAP2 p.Ser153Gly (c.457A>G) in the general population?

CKAP2 p.Ser153Gly (c.457A>G) is very rare (popmax 0.00932%, nfe) (gnomAD).

What do computational predictors say about CKAP2 p.Ser153Gly (c.457A>G)?

AlphaMissense predicts likely benign (score 0.0636) — an in-silico prediction, not a clinical call.

CKAP2 p.Ser153Gly

c.457A>G · VCV4229214

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0636 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00932%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0636	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -8.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -0.69
Regional constraint	o/e 1.06	unconstrained · MANE · 6,978 bp · p 0.17 · regional, not allelic
Overall
CADD	9.169	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S154G vs ClinVar S153G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00932% European (non-Finnish) · 110/1,179,972 alleles

Filtering AF 0.00791% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00736%

Overall 0.00744% 120/1,613,662 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,940
European (non-Finnish)grpmax	0.00932%	10,727
East Asian	0.00223%	44,890

Remaining individuals 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: CKAP2
Protein: p.Ser153Gly
Coding: c.457A>G
MANE Select: NM_018204
Type: single nucleotide variant
Location: chr13:52461283 (GRCh38)
Gene constraint: LOEUF 0.983 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.29
Residue 153: the 'disordered' region

Full CKAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CKAP2 p.Arg628Gln Uncertain significance ★★ ⚠ same type
CKAP2 p.Asn386Asp Benign ★★ same type
CKAP2 p.Thr312= Benign ★★ same type
CKAP2 p.Ala214Ser Uncertain significance ★ ⚠ same type
CKAP2 p.Ala326Thr Uncertain significance ★ ⚠ same type
CKAP2 p.Ala347Ser Uncertain significance ★ ⚠ same type
CKAP2 p.Ala350Thr Uncertain significance ★ ⚠ same type
CKAP2 p.Ala614Ser 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/ckap2-p-ser153gly (accessed [today's date]).

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