Is ABCB8 p.Ser39Arg (c.115A>C) pathogenic?

ABCB8 p.Ser39Arg (c.115A>C) is classified Uncertain significance in ABCB8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.1376); Absent from gnomAD v4.1.

How common is ABCB8 p.Ser39Arg (c.115A>C) in the general population?

ABCB8 p.Ser39Arg (c.115A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB8 p.Ser39Arg (c.115A>C)?

AlphaMissense predicts likely benign (score 0.1376) — an in-silico prediction, not a clinical call.

ABCB8 p.Ser39Arg

c.115A>C · VCV4636102

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1376 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1376	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.01	GERP -1.9
Regional constraint	o/e 0.93	unconstrained · MANE · 17 kb · p 0.036 · regional, not allelic
Overall
CADD	1.462	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 S56R vs ClinVar S39R) — 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.Ser39Arg
Coding: c.115A>C
MANE Select: NM_007188
Type: single nucleotide variant
Location: chr7:151033624 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 2 PDB

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

Similar variants

ABCB8 p.Ser39Asn Benign ★★ 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.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-ser39arg (accessed [today's date]).

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