Is ABCB8 p.Ser174Pro (c.520T>C) pathogenic?

ABCB8 p.Ser174Pro (c.520T>C) is classified Uncertain significance in ABCB8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely pathogenic (0.763); Absent from gnomAD v4.1.

How common is ABCB8 p.Ser174Pro (c.520T>C) in the general population?

ABCB8 p.Ser174Pro (c.520T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB8 p.Ser174Pro (c.520T>C)?

AlphaMissense predicts likely pathogenic (score 0.763) — an in-silico prediction, not a clinical call.

ABCB8 p.Ser174Pro

c.520T>C · VCV3977868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.763 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.763	likely pathogenic
REVEL	0.585	indeterminate
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 17 kb · p 0.036 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S191P vs ClinVar S174P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCB8
Protein: p.Ser174Pro
Coding: c.520T>C
MANE Select: NM_007188
Type: single nucleotide variant
Location: chr7:151034384 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 2 PDB
Residue 174: an α-helix; the abc transmembrane type-1 domain

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

Similar variants

ABCB8 p.Ser174Phe Uncertain significance ★ same residue
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

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-ser174pro (accessed [today's date]).

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