Is SCARB1 p.Ser76= (c.228C>T) pathogenic?

SCARB1 p.Ser76= (c.228C>T) is classified Benign in SCARB1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-07-02). Rare (popmax 0.22%, afr).

How common is SCARB1 p.Ser76= (c.228C>T) in the general population?

SCARB1 p.Ser76= (c.228C>T) is rare (popmax 0.22%, afr) (gnomAD).

SCARB1 p.Ser76=

c.228C>T · rs146377057 · VCV2770657

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.22%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -3.3
Overall
CADD	0.054	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.22% African / African-American · 165/75,048 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.182%

Overall 0.0126% 203/1,614,212 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.22%	455
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.00666%	15,005
European (non-Finnish)	0.00229%	43,705

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: SCARB1
Protein: p.Ser76=
Coding: c.228C>T
MANE Select: NM_005505
dbSNP: rs146377057
Type: single nucleotide variant
Location: chr12:124817606 (GRCh38)
Gene constraint: LOEUF 0.71 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.25

Full SCARB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCARB1 p.Arg45Cys Uncertain significance ★★ ⚠ same type
SCARB1 p.Lys482Asn Uncertain significance ★★ same type
SCARB1 p.Met136Lys Uncertain significance ★★ ⚠ same type
SCARB1 p.Pro48Ala Uncertain significance ★★ ⚠ same type
SCARB1 c.1128+73C>A Benign ★★ same type
SCARB1 c.1202+80G>A Likely benign ★★ same type
SCARB1 c.1255-41C>G Benign ★★ same type
SCARB1 c.1255-52T>G Benign ★★ 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/scarb1-p-ser76 (accessed [today's date]).

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