Is CBARP p.Arg144His (c.431G>A) pathogenic?

CBARP p.Arg144His (c.431G>A) is classified Uncertain significance in CBARP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: likely benign (0.1118); Ultra-rare (popmax 0.0227%, afr).

How common is CBARP p.Arg144His (c.431G>A) in the general population?

CBARP p.Arg144His (c.431G>A) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about CBARP p.Arg144His (c.431G>A)?

AlphaMissense predicts likely benign (score 0.1118) — an in-silico prediction, not a clinical call.

CBARP p.Arg144His

c.431G>A · rs370902462 · VCV2234837

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1118 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1118	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.87	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 0.35	GERP -2.3, phastCons 0.023
Regional constraint	o/e 1.17	unconstrained · MANE · 6,918 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	24.1	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 0.0227% African / African-American · 17/74,812 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00373% 60/1,609,256 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,401
Middle Eastern	0.0172%	5,828
East Asian	0.0067%	14,934
Remaining individualsnot grpmax-eligible	0.00482%	20,748
European (non-Finnish)	0.00297%	33,656
South Asian	0.0011%	90,930

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: CBARP
Protein: p.Arg144His
Coding: c.431G>A
MANE Select: NM_001393918
dbSNP: rs370902462
Type: single nucleotide variant
Location: chr19:1235025 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.23

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

Similar variants

CBARP p.Arg535= Likely benign ★★ same type
CBARP c.1154+114C>G Uncertain significance ★ same type
CBARP c.1154+126G>T Uncertain significance ★ same type
CBARP c.1154+36C>G Uncertain significance ★ same type
CBARP c.1154+45C>T Uncertain significance ★ same type
CBARP c.1154+80G>A Uncertain significance ★ same type
CBARP c.1154+87C>T Uncertain significance ★ same type
CBARP p.Ala19Val 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/cbarp-p-arg144his (accessed [today's date]).

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