Is ABCG1 p.Phe448= (c.1344C>T) pathogenic?

ABCG1 p.Phe448= (c.1344C>T) is classified Likely benign in ABCG1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-23). Rare (popmax 0.122%, nfe); Associated with ABCG1-related disorder.

What condition is associated with ABCG1 p.Phe448= (c.1344C>T)?

ABCG1 p.Phe448= (c.1344C>T) is associated with ABCG1-related disorder (ClinVar).

How common is ABCG1 p.Phe448= (c.1344C>T) in the general population?

ABCG1 p.Phe448= (c.1344C>T) is rare (popmax 0.122%, nfe) (gnomAD).

ABCG1 p.Phe448=

c.1344C>T · rs138421137 · VCV3039074

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.122%, nfe)

Conditions

ABCG1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.362	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 2.2, phastCons 1
Overall
CADD	12.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.122% European (non-Finnish) · 1,441/1,180,036 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.115%

Overall 0.122% 1,970/1,614,198 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.695%	144
European (non-Finnish)grpmax	0.122%	819
Remaining individualsnot grpmax-eligible	0.0752%	1,330
South Asian	0.0187%	5,358
African / African-American	0.0173%	5,772
Admixed American	0.00833%	12,004
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
East Asian	0.00223%	44,882

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ABCG1
Protein: p.Phe448=
Coding: c.1344C>T
MANE Select: NM_016818
dbSNP: rs138421137
Type: single nucleotide variant
Location: chr21:42290169 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 81.34 · 5 PDB
Residue 448: the abc transmembrane type-2 domain

Full ABCG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCG1-related disorder

Similar variants

ABCG1 p.Phe640Leu Uncertain significance ⚠ same condition
ABCG1 c.538-6C>T Benign same condition
ABCG1 p.Ala203= Likely benign same condition
ABCG1 p.Asp614= Likely benign same condition
ABCG1 p.Cys3= Benign same condition
ABCG1 p.Gly331= Benign same condition
ABCG1 p.Gly358Arg Benign same condition
ABCG1 p.Leu113= 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/abcg1-p-phe448 (accessed [today's date]).

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