Is ABCC9 p.Ser1020Pro (c.3058T>C) pathogenic?

ABCC9 p.Ser1020Pro (c.3058T>C) is classified Pathogenic in ABCC9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2012-05-18). AlphaMissense: likely pathogenic (0.9397); Absent from gnomAD v4.1; Associated with hypertrichotic osteochondrodysplasia Cantu type.

What condition is associated with ABCC9 p.Ser1020Pro (c.3058T>C)?

ABCC9 p.Ser1020Pro (c.3058T>C) is associated with hypertrichotic osteochondrodysplasia Cantu type (ClinVar).

How common is ABCC9 p.Ser1020Pro (c.3058T>C) in the general population?

ABCC9 p.Ser1020Pro (c.3058T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC9 p.Ser1020Pro (c.3058T>C)?

AlphaMissense predicts likely pathogenic (score 0.9397) — an in-silico prediction, not a clinical call.

ABCC9 p.Ser1020Pro

c.3058T>C · rs387907229 · VCV35535

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9397 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrichotic osteochondrodysplasia Cantu type

Computational evidence

Protein change
AlphaMissense	0.9397	likely pathogenic ✓ concordant with ClinVar
REVEL	0.766	pathogenic-leaning
SaProt	LLR -8.36	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 1,230 bp · p 3.5e-07 · regional, not allelic
Overall
CADD	23.9	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

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.Ser1020Pro
Coding: c.3058T>C
MANE Select: NM_020297
dbSNP: rs387907229
Type: single nucleotide variant
Location: chr12:21845641 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72
Residue 1020: the abc transmembrane type-1 2 domain; a UniProt-annotated variant site (in htocd)

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

Disease context

hypertrichotic osteochondrodysplasia Cantu type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCC9 p.Ser1020= Conflicting classifications of pathogenicity ★ same residue
ABCC9 p.Ser1020Leu Uncertain significance ★ ⚠ same residue
ABCC9 p.Arg1116Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCC9 p.Arg1116His Pathogenic ★★ ⚠ same condition
ABCC9 p.Arg1154Gln Pathogenic ★★ same condition
ABCC9 p.Arg1154Trp Pathogenic/Likely pathogenic ★★ same condition
ABCC9 p.Gly989Glu Pathogenic/Likely pathogenic ★★ same condition
ABCC9 p.Thr1202Met Pathogenic/Likely pathogenic ★★ ⚠ 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-ser1020pro (accessed [today's date]).

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