Is ABCC1 p.Arg433Ser (c.1299G>T) pathogenic?

ABCC1 p.Arg433Ser (c.1299G>T) is classified Benign in ABCC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-01). AlphaMissense: likely pathogenic (0.9686); Low-frequency (popmax 1.35%, nfe).

How common is ABCC1 p.Arg433Ser (c.1299G>T) in the general population?

ABCC1 p.Arg433Ser (c.1299G>T) is low-frequency (popmax 1.35%, nfe) (gnomAD).

What do computational predictors say about ABCC1 p.Arg433Ser (c.1299G>T)?

AlphaMissense predicts likely pathogenic (score 0.9686) — an in-silico prediction, not a clinical call.

ABCC1 p.Arg433Ser

c.1299G>T · rs60782127 · VCV489391

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9686 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.35%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9686	likely pathogenic · top 9% in ABCC1
REVEL	0.635	indeterminate
SaProt	LLR -12.82	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.19	GERP -3.5, phastCons 0.86
Regional constraint	o/e 0.88	unconstrained · MANE · 97 kb · p 2.5e-06 · regional, not allelic
Overall
CADD	22.9	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 1.35% European (non-Finnish) · 15,922/1,180,036 alleles

Filtering AF 1.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.32%

Overall 1.13% 18,268/1,614,196 alleles · low-frequency exomes 17,119/1,461,886 · genomes 1,149/152,310 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.35%	74
Ashkenazi Jewishnot grpmax-eligible	1.28%	78
Finnishnot grpmax-eligible	1.08%	92
Amishnot grpmax-eligible	0.987%	101
Remaining individualsnot grpmax-eligible	0.974%	103
Admixed American	0.423%	236
Middle Eastern	0.363%	276
South Asian	0.261%	383
African / African-American	0.187%	536
East Asian	0.00223%	44,880

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.Arg433Ser
Coding: c.1299G>T
MANE Select: NM_004996
dbSNP: rs60782127
Type: single nucleotide variant
Location: chr16:16048222 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 5 PDB
Residue 433: the abc transmembrane type-1 1 domain; a UniProt-annotated variant site (in)

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.Asp637= Likely benign ★★ same type
ABCC1 p.Gly762= Benign/Likely benign ★★ same type
ABCC1 p.Gly885= Benign ★★ same type
ABCC1 p.Ile1484= 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-arg433ser (accessed [today's date]).

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