Is ABCB1 p.Arg1279Ser (c.3835C>A) pathogenic?

ABCB1 p.Arg1279Ser (c.3835C>A) is classified Uncertain significance in ABCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1997); Ultra-rare (popmax 0.0501%, mid).

How common is ABCB1 p.Arg1279Ser (c.3835C>A) in the general population?

ABCB1 p.Arg1279Ser (c.3835C>A) is ultra-rare (popmax 0.0501%, mid) (gnomAD).

What do computational predictors say about ABCB1 p.Arg1279Ser (c.3835C>A)?

AlphaMissense predicts likely benign (score 0.1997) — an in-silico prediction, not a clinical call.

ABCB1 p.Arg1279Ser

c.3835C>A · rs137996914 · VCV3118728

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1997 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0501%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1997	likely benign
REVEL	0.434	indeterminate
SaProt	LLR -4.54	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 1.9	GERP 0.86, phastCons 0.011
Regional constraint	o/e 0.85	unconstrained · MANE · 96 kb · p 6.7e-09 · regional, not allelic
Overall
CADD	20.2	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0501% Middle Eastern · 3/5,990 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00727%

Overall 0.000274% 4/1,461,766 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0501%	1,997
Remaining individualsnot grpmax-eligible	0.0016%	62,492

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.Arg1279Ser
Coding: c.3835C>A
MANE Select: NM_001348946
dbSNP: rs137996914
Type: single nucleotide variant
Location: chr7:87504251 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.72 · 24 PDB
Residue 1279: 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 p.Arg1279His Uncertain significance ★ ⚠ same residue
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

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-arg1279ser (accessed [today's date]).

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