Is ABCC9 p.Ser118Pro (c.352T>C) pathogenic?

ABCC9 p.Ser118Pro (c.352T>C) is classified Uncertain significance in ABCC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-26). AlphaMissense: likely pathogenic (0.9943); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ABCC9 p.Ser118Pro (c.352T>C)?

ABCC9 p.Ser118Pro (c.352T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCC9 p.Ser118Pro (c.352T>C) in the general population?

ABCC9 p.Ser118Pro (c.352T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC9 p.Ser118Pro (c.352T>C)?

AlphaMissense predicts likely pathogenic (score 0.9943) — an in-silico prediction, not a clinical call.

ABCC9 p.Ser118Pro

c.352T>C · rs2541827710 · VCV1732356

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9943 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9943	likely pathogenic · top 8% in ABCC9
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -11.38	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 29 kb · p 4.3e-29 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCC9
Protein: p.Ser118Pro
Coding: c.352T>C
MANE Select: NM_020297
dbSNP: rs2541827710
Type: single nucleotide variant
Location: chr12:21925996 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72

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.Ser118= Likely benign ★★ same residue
ABCC9 p.Ser118Leu 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

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-ser118pro (accessed [today's date]).

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