Is ABCC9 p.Leu398= (c.1194C>T) pathogenic?

ABCC9 p.Leu398= (c.1194C>T) is classified Likely benign in ABCC9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-19). Very rare (popmax 0.00172%, amr); Associated with Cardiovascular phenotype.

What condition is associated with ABCC9 p.Leu398= (c.1194C>T)?

ABCC9 p.Leu398= (c.1194C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCC9 p.Leu398= (c.1194C>T) in the general population?

ABCC9 p.Leu398= (c.1194C>T) is very rare (popmax 0.00172%, amr) (gnomAD).

ABCC9 p.Leu398=

c.1194C>T · rs1430745818 · VCV519130

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00172%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.5
Overall
CADD	2.036	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00172% Admixed American · 1/58,236 alleles

Overall 0.000188% 3/1,598,684 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00172%	58,236
Remaining individualsnot grpmax-eligible	0.00161%	62,058
European (non-Finnish)	8.51e-05%	1,175,206

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: ABCC9
Protein: p.Leu398=
Coding: c.1194C>T
MANE Select: NM_020297
dbSNP: rs1430745818
Type: single nucleotide variant
Location: chr12:21910283 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72
Residue 398: the abc transmembrane type-1 1 domain

Full ABCC9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCC9 p.Leu398Pro Uncertain significance ★ ⚠ same residue
ABCC9 c.2092+5G>T Uncertain significance ★★ same condition
ABCC9 c.3893-3C>T Uncertain significance ★★ same condition
ABCC9 c.4512+693G>A Uncertain significance ★★ ⚠ same condition
ABCC9 c.4512+733C>A Uncertain significance ★★ ⚠ same condition
ABCC9 p.Ala136Ser Uncertain significance ★★ ⚠ same condition
ABCC9 p.Ala276Thr Uncertain significance ★★ ⚠ same condition
ABCC9 p.Ala351Ser Uncertain significance ★★ ⚠ same condition

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/abcc9-p-leu398 (accessed [today's date]).

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