Is CAB39L p.Arg151Gln (c.452G>A) pathogenic?

CAB39L p.Arg151Gln (c.452G>A) is classified Uncertain significance in CAB39L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). AlphaMissense: ambiguous (0.4781); Very rare (popmax 0.00267%, afr).

How common is CAB39L p.Arg151Gln (c.452G>A) in the general population?

CAB39L p.Arg151Gln (c.452G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CAB39L p.Arg151Gln (c.452G>A)?

AlphaMissense predicts ambiguous (score 0.4781) — an in-silico prediction, not a clinical call.

CAB39L p.Arg151Gln

c.452G>A · rs757820177 · VCV3136175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4781 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.4781	ambiguous
REVEL	0.632	indeterminate
SaProt	LLR -10.67	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 72 kb · p 0.19 · regional, not allelic
Overall
CADD	32.0	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 0.00267% African / African-American · 2/74,834 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00062% 10/1,611,654 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,417
East Asian	0.00223%	44,810
South Asian	0.00221%	45,252
European (non-Finnish)	0.000424%	235,776

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: CAB39L
Protein: p.Arg151Gln
Coding: c.452G>A
MANE Select: NM_001079670
dbSNP: rs757820177
Type: single nucleotide variant
Location: chr13:49350856 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.88 · 1 PDB

Full CAB39L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAB39L p.Ala48Gly Uncertain significance ★ ⚠ same type
CAB39L p.Arg112Trp Uncertain significance ★ ⚠ same type
CAB39L p.Arg141Cys Uncertain significance ★ ⚠ same type
CAB39L p.Arg141His Uncertain significance ★ ⚠ same type
CAB39L p.Asn13Ser Uncertain significance ★ ⚠ same type
CAB39L p.Asp85Tyr Uncertain significance ★ ⚠ same type
CAB39L p.Asp96Tyr Uncertain significance ★ ⚠ same type
CAB39L p.Gln309His 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/cab39l-p-arg151gln (accessed [today's date]).

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