Is HDLBP p.Arg754= (c.2262C>T) pathogenic?

HDLBP p.Arg754= (c.2262C>T) is classified Likely benign in HDLBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Rare (popmax 0.127%, afr); Associated with HDLBP-related disorder.

What condition is associated with HDLBP p.Arg754= (c.2262C>T)?

HDLBP p.Arg754= (c.2262C>T) is associated with HDLBP-related disorder (ClinVar).

How common is HDLBP p.Arg754= (c.2262C>T) in the general population?

HDLBP p.Arg754= (c.2262C>T) is rare (popmax 0.127%, afr) (gnomAD).

HDLBP p.Arg754=

c.2262C>T · rs143039216 · VCV3039218

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.127%, afr)

Conditions

HDLBP-related disorder

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.012	strongly benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -11	GERP -3.4
Overall
CADD	0.169	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.127% African / African-American · 95/75,036 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0983%

Overall 0.00867% 140/1,614,176 alleles · rare exomes 84/1,461,874 · genomes 56/152,302 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.127%	790
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	0.00263%	38,065
Admixed American	0.00167%	60,026
South Asian	0.0011%	91,082

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: HDLBP
Protein: p.Arg754=
Coding: c.2262C>T
MANE Select: NM_005336
dbSNP: rs143039216
Type: single nucleotide variant
Location: chr2:241240030 (GRCh38)

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

Disease context

HDLBP-related disorder

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/hdlbp-p-arg754 (accessed [today's date]).

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