Is ABCB6 p.Arg648Ter (c.1942C>T) pathogenic?

ABCB6 p.Arg648Ter (c.1942C>T) is classified Uncertain significance in ABCB6 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-20). Ultra-rare (popmax 0.0117%, amr).

How common is ABCB6 p.Arg648Ter (c.1942C>T) in the general population?

ABCB6 p.Arg648Ter (c.1942C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

ABCB6 p.Arg648Ter

c.1942C>T · rs376664522 · VCV30479

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 9.8	GERP 0.98, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,988 alleles

Filtering AF 0.00859% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00803%

Overall 0.00812% 131/1,613,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,570
European (non-Finnish)	0.0101%	9,916
Remaining individualsnot grpmax-eligible	0.008%	12,495

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: ABCB6
Protein: p.Arg648Ter
Coding: c.1942C>T
MANE Select: NM_005689
dbSNP: rs376664522
Type: single nucleotide variant
Location: chr2:219212413 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 648: a β-strand; the abc transporter domain; a UniProt-annotated variant site (in)

Full ABCB6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB6 p.Arg648Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCB6 p.Ala164Thr Uncertain significance ★★ ⚠ same type
ABCB6 p.Ala57Thr Uncertain significance ★★ ⚠ same type
ABCB6 p.Ala66Thr Uncertain significance ★★ ⚠ same type
ABCB6 p.Ala681Thr Uncertain significance ★★ ⚠ same type
ABCB6 p.Arg135Ser Uncertain significance ★★ ⚠ same type
ABCB6 p.Arg439Cys Uncertain significance ★★ ⚠ same type
ABCB6 p.Arg450Gln Uncertain significance ★★ ⚠ 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/abcb6-p-arg648ter (accessed [today's date]).

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