Is ABCC1 p.Ser667= (c.2001C>T) pathogenic?

ABCC1 p.Ser667= (c.2001C>T) is classified Benign in ABCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-01). Low-frequency (popmax 1.78%, mid).

How common is ABCC1 p.Ser667= (c.2001C>T) in the general population?

ABCC1 p.Ser667= (c.2001C>T) is low-frequency (popmax 1.78%, mid) (gnomAD).

ABCC1 p.Ser667=

c.2001C>T · VCV4083528

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.78%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.44	acceptor gain · deltas
Pangolin	Δ0.41	gain · loss 0.11 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.48	GERP -3.4
Overall
CADD	16.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.78% Middle Eastern · 108/6,058 alleles

Filtering AF 1.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.41%

Overall 1.31% 21,097/1,613,984 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.62%	38
Ashkenazi Jewishnot grpmax-eligible	1.96%	51
Middle Easterngrpmax	1.78%	56
European (non-Finnish)	1.38%	72
Remaining individualsnot grpmax-eligible	1.34%	74
African / African-American	1.07%	94
Admixed American	0.921%	109
East Asian	0.305%	328
South Asian	0.132%	759

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ABCC1
Protein: p.Ser667=
Coding: c.2001C>T
MANE Select: NM_004996
Type: single nucleotide variant
Location: chr16:16079364 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 5 PDB
Residue 667: a β-strand; the abc transporter 1 domain

Full ABCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC1 p.Thr1464Met Uncertain significance ★★ ⚠ same type
ABCC1 c.1381-5C>G Benign ★★ same type
ABCC1 p.Ala1260= Benign ★★ same type
ABCC1 p.Ala1406= Benign ★★ same type
ABCC1 p.Arg433Ser Benign ★★ same type
ABCC1 p.Asp637= Likely benign ★★ same type
ABCC1 p.Gly762= Benign/Likely benign ★★ same type
ABCC1 p.Gly885= 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/abcc1-p-ser667 (accessed [today's date]).

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