Is ABCB8 p.Glu575Lys (c.1723G>A) pathogenic?

ABCB8 p.Glu575Lys (c.1723G>A) is classified Uncertain significance in ABCB8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-22). AlphaMissense: likely benign (0.0969); Ultra-rare (popmax 0.055%, amr).

How common is ABCB8 p.Glu575Lys (c.1723G>A) in the general population?

ABCB8 p.Glu575Lys (c.1723G>A) is ultra-rare (popmax 0.055%, amr) (gnomAD).

What do computational predictors say about ABCB8 p.Glu575Lys (c.1723G>A)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

ABCB8 p.Glu575Lys

c.1723G>A · rs150297725 · VCV3125904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0969 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.055%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0969	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -7.02	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 5	GERP -0.49, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 17 kb · p 0.036 · regional, not allelic
Overall
CADD	18.44	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E592K vs ClinVar E575K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.055% Admixed American · 33/60,022 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0351%

Overall 0.00434% 70/1,613,160 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.055%	1,819
African / African-American	0.028%	3,574
East Asian	0.00891%	11,222
Remaining individualsnot grpmax-eligible	0.0064%	15,623
European (non-Finnish)	0.000678%	147,498

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: ABCB8
Protein: p.Glu575Lys
Coding: c.1723G>A
MANE Select: NM_007188
dbSNP: rs150297725
Type: single nucleotide variant
Location: chr7:151042066 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 2 PDB
Residue 575: the abc transporter domain

Full ABCB8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB8 c.564+4C>T Benign ★★ same type
ABCB8 p.Ala101= Benign ★★ same type
ABCB8 p.Arg452Leu Benign ★★ ⚠ same type
ABCB8 p.His201= Benign ★★ same type
ABCB8 p.Leu124Val Benign ★★ same type
ABCB8 p.Ser39Asn Benign ★★ ⚠ same type
ABCB8 p.Val110= Benign ★★ same type
ABCB8 p.Val633= 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/abcb8-p-glu575lys (accessed [today's date]).

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