Is CKAP2L p.Ser129Pro (c.385T>C) pathogenic?

CKAP2L p.Ser129Pro (c.385T>C) is classified Benign/Likely benign in CKAP2L (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-09). AlphaMissense: likely benign (0.0944); Rare (popmax 0.271%, nfe).

How common is CKAP2L p.Ser129Pro (c.385T>C) in the general population?

CKAP2L p.Ser129Pro (c.385T>C) is rare (popmax 0.271%, nfe) (gnomAD).

What do computational predictors say about CKAP2L p.Ser129Pro (c.385T>C)?

AlphaMissense predicts likely benign (score 0.0944) — an in-silico prediction, not a clinical call.

CKAP2L p.Ser129Pro

c.385T>C · rs115154628 · VCV779406

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0944 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.271%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0944	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -7.82	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 1.8	GERP -1.1, phastCons 0.13
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.21 · regional, not allelic
Overall
CADD	15.8	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 0.271% European (non-Finnish) · 3,192/1,180,036 alleles

Filtering AF 0.263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.259%

Overall 0.212% 3,430/1,614,192 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.271%	370
Remaining individualsnot grpmax-eligible	0.138%	727
South Asian	0.067%	1,493
Admixed American	0.0666%	1,500
African / African-American	0.0573%	1,745
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
Finnishnot grpmax-eligible	0.00625%	16,009

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.Ser129Pro
Coding: c.385T>C
MANE Select: NM_152515
dbSNP: rs115154628
Type: single nucleotide variant
Location: chr2:112756986 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68
Residue 129: the 'disordered' region

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

Similar variants

CKAP2L p.Arg206Gly Uncertain significance ★★ ⚠ same type
CKAP2L p.Arg284Trp Uncertain significance ★★ ⚠ same type
CKAP2L p.Arg347Lys Uncertain significance ★★ ⚠ same type
CKAP2L p.Arg688Gln Uncertain significance ★★ ⚠ same type
CKAP2L p.Cys725Ser Uncertain significance ★★ ⚠ same type
CKAP2L p.Gln428Arg Uncertain significance ★★ ⚠ same type
CKAP2L p.Glu462Val Uncertain significance ★★ ⚠ same type
CKAP2L p.Ile283Leu 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/ckap2l-p-ser129pro (accessed [today's date]).

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