Is ABCB1 p.Ser1022Arg (c.3066C>A) pathogenic?

ABCB1 p.Ser1022Arg (c.3066C>A) is classified Uncertain significance in ABCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). AlphaMissense: ambiguous (0.4715); Very rare (popmax 0.00329%, sas).

How common is ABCB1 p.Ser1022Arg (c.3066C>A) in the general population?

ABCB1 p.Ser1022Arg (c.3066C>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ABCB1 p.Ser1022Arg (c.3066C>A)?

AlphaMissense predicts ambiguous (score 0.4715) — an in-silico prediction, not a clinical call.

ABCB1 p.Ser1022Arg

c.3066C>A · rs1158715642 · VCV2314483

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4715 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4715	ambiguous
REVEL	0.222	benign-leaning
SaProt	LLR -11.16	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.11, phastCons 0.99
Regional constraint	o/e 0.85	unconstrained · MANE · 96 kb · p 6.7e-09 · regional, not allelic
Overall
CADD	20.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,088 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000205% 3/1,461,874 alleles · very rare

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: ABCB1
Protein: p.Ser1022Arg
Coding: c.3066C>A
MANE Select: NM_001348946
dbSNP: rs1158715642
Type: single nucleotide variant
Location: chr7:87516527 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.72 · 24 PDB
Residue 1022: a UniProt-annotated variant site (in enpat; likely pathogenic)

Full ABCB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB1 c.287-25G>T Benign ★★ same type
ABCB1 p.Ala1132= Benign/Likely benign ★★ same type
ABCB1 p.Gln1107Pro Benign/Likely benign ★★ same type
ABCB1 p.Glu243= Benign/Likely benign ★★ same type
ABCB1 p.Glu618= Likely benign ★★ same type
ABCB1 p.Gly412= Benign ★★ same type
ABCB1 p.Ile1145= Benign ★★ same type
ABCB1 p.Ile261Val 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/abcb1-p-ser1022arg (accessed [today's date]).

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