Is ABCC9 p.Ala940Ser (c.2818G>T) pathogenic?

ABCC9 p.Ala940Ser (c.2818G>T) is classified Uncertain significance in ABCC9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-10). AlphaMissense: likely benign (0.3253); Very rare (popmax 8.48e-05%, nfe); Associated with intellectual disability and myopathy syndrome.

What condition is associated with ABCC9 p.Ala940Ser (c.2818G>T)?

ABCC9 p.Ala940Ser (c.2818G>T) is associated with intellectual disability and myopathy syndrome, hypertrichotic osteochondrodysplasia Cantu type, dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Ala940Ser (c.2818G>T) in the general population?

ABCC9 p.Ala940Ser (c.2818G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ABCC9 p.Ala940Ser (c.2818G>T)?

AlphaMissense predicts likely benign (score 0.3253) — an in-silico prediction, not a clinical call.

ABCC9 p.Ala940Ser

c.2818G>T · rs1373377020 · VCV1009218

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3253 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability and myopathy syndrome

Computational evidence

Protein change
AlphaMissense	0.3253	likely benign
REVEL	0.418	indeterminate
SaProt	LLR -3.81	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 6,731 bp · p 0.0027 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,636 alleles

Overall 6.84e-05% 1/1,461,314 alleles · very rare

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.Ala940Ser
Coding: c.2818G>T
MANE Select: NM_020297
dbSNP: rs1373377020
Type: single nucleotide variant
Location: chr12:21848198 (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

intellectual disability and myopathy syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrichotic osteochondrodysplasia Cantu type dilated cardiomyopathy 1O atrial fibrillation, familial, 12

Similar variants

ABCC9 c.2506-1G>A Pathogenic/Likely pathogenic ★★ same condition
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.Gln852Ter 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-ala940ser (accessed [today's date]).

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