Is CAB39 p.Lys10Arg (c.29A>G) pathogenic?

CAB39 p.Lys10Arg (c.29A>G) is classified Uncertain significance in CAB39 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-26). AlphaMissense: likely benign (0.087); Ultra-rare (popmax 0.0134%, eas).

How common is CAB39 p.Lys10Arg (c.29A>G) in the general population?

CAB39 p.Lys10Arg (c.29A>G) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CAB39 p.Lys10Arg (c.29A>G)?

AlphaMissense predicts likely benign (score 0.087) — an in-silico prediction, not a clinical call.

CAB39 p.Lys10Arg

c.29A>G · VCV3262614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.087 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.087	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -6.53	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 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 59 kb · p 6e-11 · regional, not allelic
Overall
CADD	23.0	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 0.0134% East Asian · 6/44,888 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00285% 46/1,613,392 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,481
Remaining individualsnot grpmax-eligible	0.008%	12,492
South Asian	0.00439%	22,763
African / African-American	0.004%	24,969
Admixed American	0.00333%	29,991
European (non-Finnish)	0.00212%	47,180
Finnishnot grpmax-eligible	0.00156%	64,034

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: CAB39
Protein: p.Lys10Arg
Coding: c.29A>G
MANE Select: NM_016289
Type: single nucleotide variant
Location: chr2:230760030 (GRCh38)
Gene constraint: LOEUF 0.693 · pLI 0.67 (gnomAD)
Structure: AlphaFold pLDDT 94.77 · 10 PDB

Full CAB39 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAB39 p.Asp239Glu Uncertain significance ★ ⚠ same type
CAB39 p.Gln69Pro Uncertain significance ★ ⚠ same type
CAB39 p.Ile110Thr Uncertain significance ★ ⚠ same type
CAB39 p.Ile303Met Uncertain significance ★ ⚠ same type
CAB39 p.Leu296Phe Uncertain significance ★ ⚠ same type
CAB39 p.Met50Val Uncertain significance ★ ⚠ same type
CAB39 p.Phe185Tyr Uncertain significance ★ ⚠ same type
CAB39 p.Phe210Leu 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/cab39-p-lys10arg (accessed [today's date]).

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