Is ABCC12 p.Arg599Trp (c.1795C>T) pathogenic?

ABCC12 p.Arg599Trp (c.1795C>T) is classified Uncertain significance in ABCC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely benign (0.1861); Ultra-rare (popmax 0.0495%, sas).

How common is ABCC12 p.Arg599Trp (c.1795C>T) in the general population?

ABCC12 p.Arg599Trp (c.1795C>T) is ultra-rare (popmax 0.0495%, sas) (gnomAD).

What do computational predictors say about ABCC12 p.Arg599Trp (c.1795C>T)?

AlphaMissense predicts likely benign (score 0.1861) — an in-silico prediction, not a clinical call.

ABCC12 p.Arg599Trp

c.1795C>T · rs762026626 · VCV2221296

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1861 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1861	likely benign
REVEL	0.773	moderately pathogenic-leaning
SaProt	LLR -12.89	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.1	GERP -2.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.2 · regional, not allelic
Overall
CADD	22.2	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 0.0495% South Asian · 45/90,966 alleles

Filtering AF 0.0379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.00384% 62/1,612,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.00641%	15,613
African / African-American	0.00534%	18,731
European (non-Finnish)	0.000763%	131,057

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: ABCC12
Protein: p.Arg599Trp
Coding: c.1795C>T
MANE Select: NM_001393797
dbSNP: rs762026626
Type: single nucleotide variant
Location: chr16:48115609 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.09
Residue 599: the abc transporter 1 domain

Full ABCC12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC12 p.Arg599Gln Uncertain significance ★ ⚠ same residue
ABCC12 p.Thr1080Ala Uncertain significance ★★ ⚠ same type
ABCC12 p.Arg122= Likely benign ★★ same type
ABCC12 p.Gln831Ter Likely benign ★★ same type
ABCC12 p.Glu1191Ala Benign ★★ same type
ABCC12 p.Gly164Ter Benign/Likely benign ★★ same type
ABCC12 p.Lys1344= Benign ★★ same type
ABCC12 p.Lys894Met 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/abcc12-p-arg599trp (accessed [today's date]).

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