Is HDLBP p.Ser262= (c.786C>T) pathogenic?

HDLBP p.Ser262= (c.786C>T) is classified Likely benign in HDLBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-25). Ultra-rare (popmax 0.034%, sas); Associated with HDLBP-related disorder.

What condition is associated with HDLBP p.Ser262= (c.786C>T)?

HDLBP p.Ser262= (c.786C>T) is associated with HDLBP-related disorder (ClinVar).

How common is HDLBP p.Ser262= (c.786C>T) in the general population?

HDLBP p.Ser262= (c.786C>T) is ultra-rare (popmax 0.034%, sas) (gnomAD).

HDLBP p.Ser262=

c.786C>T · rs754361840 · VCV3047869

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, sas)

Conditions

HDLBP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.041	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5	GERP -4.1
Overall
CADD	5.695	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.034% South Asian · 31/91,082 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.019% 307/1,614,132 alleles · ultra-rare exomes 300/1,461,866 · genomes 7/152,266 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.034%	2,938
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.0224%	4,470
Remaining individualsnot grpmax-eligible	0.016%	6,251

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.Ser262=
Coding: c.786C>T
MANE Select: NM_005336
dbSNP: rs754361840
Type: single nucleotide variant
Location: chr2:241256271 (GRCh38)
Gene constraint: LOEUF 0.283 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.80 · 8 PDB
Residue 262: the kh 2 domain

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

Disease context

HDLBP-related disorder

Similar variants

HDLBP p.Pro261Leu Uncertain significance ★ ⚠ same condition
HDLBP c.1081-10A>G Benign same condition
HDLBP c.-16A>T Likely benign same condition
HDLBP c.-27G>A Likely benign same condition
HDLBP p.Ala5= Likely benign same condition
HDLBP p.Asn418Ser Benign same condition
HDLBP p.Asp190= Likely benign same condition
HDLBP p.Ile702= Likely benign same condition

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-ser262 (accessed [today's date]).

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