Is ABCB1 p.Ile261Val (c.781A>G) pathogenic?

ABCB1 p.Ile261Val (c.781A>G) is classified Benign in ABCB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-10-30). AlphaMissense: likely benign (0.0853); Low-frequency (popmax 1.66%, afr).

How common is ABCB1 p.Ile261Val (c.781A>G) in the general population?

ABCB1 p.Ile261Val (c.781A>G) is low-frequency (popmax 1.66%, afr) (gnomAD).

What do computational predictors say about ABCB1 p.Ile261Val (c.781A>G)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

ABCB1 p.Ile261Val

c.781A>G · rs36008564 · VCV711479

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.66%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.258	benign-leaning
SaProt	LLR -7.42	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 -0.04	GERP -0.69, phastCons 0.002
Regional constraint	o/e 0.85	unconstrained · MANE · 96 kb · p 6.7e-09 · regional, not allelic
Overall
CADD	14.84	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 1.66% African / African-American · 1,247/75,062 alleles

Filtering AF 1.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.55%

Overall 0.177% 2,856/1,614,096 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.66%	60
Ashkenazi Jewishnot grpmax-eligible	0.767%	130
Middle Eastern	0.743%	135
Admixed American	0.435%	230
Remaining individualsnot grpmax-eligible	0.378%	265
European (non-Finnish)	0.0685%	1,460
South Asian	0.0329%	3,036
Finnishnot grpmax-eligible	0.00312%	32,022

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.Ile261Val
Coding: c.781A>G
MANE Select: NM_001348946
dbSNP: rs36008564
Type: single nucleotide variant
Location: chr7:87561309 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.72 · 24 PDB
Residue 261: the abc transmembrane type-1 1 domain; a UniProt-annotated variant site (in); an α-helix

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.Ile598= Likely 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-ile261val (accessed [today's date]).

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