Is CKAP2L p.Ser88Phe (c.263C>T) pathogenic?

CKAP2L p.Ser88Phe (c.263C>T) is classified Uncertain significance in CKAP2L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely benign (0.1127); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with CKAP2L p.Ser88Phe (c.263C>T)?

CKAP2L p.Ser88Phe (c.263C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CKAP2L p.Ser88Phe (c.263C>T) in the general population?

CKAP2L p.Ser88Phe (c.263C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CKAP2L p.Ser88Phe (c.263C>T)?

AlphaMissense predicts likely benign (score 0.1127) — an in-silico prediction, not a clinical call.

CKAP2L p.Ser88Phe

c.263C>T · VCV4229217

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1127 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1127	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -6.66	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 2	GERP 1.5, phastCons 0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.21 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00134% African / African-American · 1/74,904 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,614,018 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-Americangrpmax	0.00134%	74,904
European (non-Finnish)	0.000424%	236,008

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: CKAP2L
Protein: p.Ser88Phe
Coding: c.263C>T
MANE Select: NM_152515
Type: single nucleotide variant
Location: chr2:112757108 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68
Residue 88: the 'disordered' region

Full CKAP2L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CKAP2L p.Ser88Pro Uncertain significance ★ ⚠ same residue
CKAP2L p.Arg206Gly Uncertain significance ★★ ⚠ same condition
CKAP2L p.Arg284Trp Uncertain significance ★★ ⚠ same condition
CKAP2L p.Arg688Gln Uncertain significance ★★ ⚠ same condition
CKAP2L p.Gln428Arg Uncertain significance ★★ ⚠ same condition
CKAP2L p.Ile283Leu Uncertain significance ★★ ⚠ same condition
CKAP2L p.Lys421Arg Uncertain significance ★★ ⚠ same condition
CKAP2L p.Lys480Glu Uncertain significance ★★ ⚠ same condition

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/ckap2l-p-ser88phe (accessed [today's date]).

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